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Treatment News 2016

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Tenofovir Resistance May Develop in More Than Half of Patients Failing Treatment in Sub-Saharan Africa.04/02/16

Published at Aidsmap

Written by Keith Alcorn

1 February 2016


 

More than half of people who experienced failure of a tenofovir-based antiretroviral regimen in sub-Saharan Africa had resistance to tenofovir, a meta-analysis of drug resistance studies published in Lancet Infectious Diseases has shown.

The study found that the prevalence of tenofovir resistance after first-line failure ranged from 20% in Western Europe and North America to 56% - 60% in sub-Saharan Africa.

The authors say that their findings suggest that somewhere between 7.5% and 17.5% of people who start treatment in sub-Saharan Africa, with a regimen composed of tenofovir, efavirenz and either lamivudine or emtricitabine, will develop tenofovir resistance after one year, based on current rates of treatment failure. This projection assumes a treatment failure rate of between 15% and 35%, depending on how it is measured, and is in line with recent WHO estimates.

This study does not reflect the prevalence of HIV drug resistance in all people on treatment, nor the prevalence of drug resistance in people who have not yet started treatment, but only the prevalence of drug resistance in people who started specific drug regimens and subsequently experienced virological failure of that treatment regimen.

The TenoRes Study

The TenoRes collaborative study was designed to assess the prevalence of tenofovir resistance in people experiencing failure of first-line treatment. Tenofovir is a recommended component of first-line antiretroviral regimens in World Health Organization HIV treatment guidelines and in European and United States treatment guidelines.

The study took data from 44 treatment cohorts in 26 countries in North America (3 studies), Europe (13 studies), Latin America (4 studies), Asia (3 studies) and sub-Saharan Africa (24 studies, sub-divided into 4 studies in the East African region, 10 studies in the Southern African region and 7 studies in West and Central Africa) where drug resistance data were available after first-line treatment failure. Participant data were eligible for inclusion in the analysis where virological failure had occurred more than four months after beginning first-line antiretroviral treatment consisting of tenofovir plus either lamivudine or emtricitabine, and a non-nucleoside reverse transcriptase inhibitor (either efavirenz or nevirapine).

The researchers carried out a series of analyses designed to identify regional, demographic and disease-specific differences in the risk of developing resistance to tenofovir and to other drugs in the failing regimen in the 44 cohort studies, comprising 1926 people.

They calculated country-level and regional risks of developing tenofovir resistance in order to take into account potential confounding factors such as differences in the delivery of care between treatment facilities or countries.

The meta-analysis found a wide variation in pre-treatment CD4 cell count between regions, from 44 cells/mm3 in Latin America and 89-104 cells/mm3 in the African regions, to 199 cells/mm3 in Western Europe. The variation in baseline viral load was most pronounced within sub-Saharan Africa, ranging from 4.8 log10 (63,000) copies in southern Africa to 5.58 log10 (316,000) copies/ml in Eastern Africa. Pre-treatment viral load was significantly higher in Eastern and Western/Central Africa and in Latin America compared to other regions.

Tenofovir resistance more frequent at CD4 counts below 100

The analysis showed that regardless of region, tenofovir resistance was associated with a lower pre-treatment CD4 cell count. People who started treatment with a CD4 cell count below 100 cells/mm3 were 50% more likely to develop resistance after treatment failure, but this difference did not seem to be driven by viral load. There was no significant difference in the risk of developing tenofovir resistance between people with baseline viral load above or below 100,000 copies/ml, nor in the risk of developing tenofovir resistance according to viral load at treatment failure.

However, the difference in the risk of tenofovir resistance according to baseline CD4 cell count was largely driven by two regions, Southern Africa and North America. Whereas there was no significant difference in the risk of tenofovir resistance in people with pre-treatment CD4 cell counts below 100 cells/mm3 in most regions, the risk of developing tenofovir resistance was 27% higher in Southern Africa (odds ratio 1.27, 95% confidence interval 1.09-1.48) and 34% higher in North America (OR 1.34, 95% CI 1.06-1.69) among people with CD4 cell counts below 100 compared to those starting treatment with CD4 cell counts above 100.

Although researchers suggest that the regional difference in tenofovir resistance is due to less frequent viral load monitoring, they also found a significant difference in the development of tenofovir resistance according to viral subtype and the other elements of the regimen, factors which also vary from one region to another.

In the case of viral subtype, the researchers found that people with subtype C virus (which predominates in Southern Africa) were 2.44 times more likely to develop tenofovir resistance after treatment failure compared to people with other non-B subtypes (OR 2.44, 95% CI 1.66-3.59). To reduce the effect of confounding factors the researchers restricted this analysis to patients receiving care in Western Europe and to non-B subtypes found in migrant populations in order to reduce any bias caused by the health system or by socio-economic factors.

Tenofovir resistance more frequent when taken with lamivudine or nevirapine

Considering the other elements of the antiretroviral regimen at the time of treatment failure, the researchers made two findings that may explain regional variations in tenofovir resistance. They found that people taking nevirapine were almost 50% more likely to develop resistance to tenofovir than people taking efavirenz (OR 1.46, (%% CI 1.28-1.67), and almost 50% more likely to develop resistance to tenofovir if they received lamivudine rather than emtricitabine (OR 1.48, 95% CI 1.20-1.82).

These findings suggest that, in studies where the median year of initiation of antiretroviral therapy was between 2008 and 2011, what is being detected is as much an effect of the use of out-of-date treatment regimens as it is an effect of late treatment initiation – both of which have been strongly warned against in updated WHO treatment guidelines since 2013. Guidelines now identify efavirenz as the preferred agent over nevirapine, and recommend treatment initiation before the CD4 cell count falls below 350 cells/mm3 – and preferably soon after diagnosis, regardless of CD4 cell count.

In the case of lamivudine WHO guidelines have been less firm, with an update in 2014 noting that studies suggest clinical equivalence. Since then a Dutch cohort study of 4740 people has shown a doubling of the risk of virological failure in people taking lamivudine compared to emtricitabine, and the risk was more pronounced in people taking nevirapine than in those taking efavirenz. 

The TenoRes study also found that of those who developed tenofovir resistance, 83% developed the M184V mutation conferring resistance to lamivudine and emtricitabine, and 78% developed resistance to nevirapine and efavirenz.

The findings indicate the need for further options for first-line treatment, say the authors, and also for second-line treatment, where WHO guidelines recommend the recycling of tenofovir. Improving access to viral load testing, increasing the frequency of viral load tests and development of cost-effective resistance screening could also contribute to reducing resistance.

The researchers also raised concerns about the possibility of onward transmission of tenofovir-resistant virus, and its impact on first-line treatment for the newly infected and tenofovir-containing pre-exposure prophylaxis for prevention of HIV infection.

"If resistant strains of HIV were significantly less effective at spreading in people, we would expect to see lower levels of the virus in patients with the resistant strain," said Dr Ravindra Gupta of University College London. "However, we found that virus levels were no lower in individuals with the resistant strain and were high enough to be fully infectious. We certainly cannot dismiss the possibility that resistant strains can spread between people and should not be complacent. We are now conducting further studies to get a more detailed picture of how tenofovir resistant viruses develop and spread."

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Treatment News 2015

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Response to WHO HIV Treatment Guidelines. 03/12/2015

Published at itcpglobal.org

1 December 2015


On World AIDS Day 2015, treatment activists celebrate the achievements made in the global fight against AIDS. Ambitious goals have been set that aim to achieve 90% of people living with HIV knowing their status, 90% of those who know their HIV status being on sustained antiretroviral therapy and 90% of those to be virally suppressed by 2020. The 2015 World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection, issued today, is an important step towards reaching those targets.

The International Treatment Preparedness Coalition (ITPC), AIDS & Rights Alliance for Southern Africa (ARASA) and the Asia Pacific Network of People Living with HIV/AIDS (APN+) welcome the new WHO HIV treatment guidelines, but would like to underline three issues that represent barriers to continued progress.

  • Community-led treatment education is inadequately supported and needs to be scaled up;
  • People living in middle income countries are denied affordable access to essential medicines, such as dolutegravir;
  • Availability of routine viral load monitoring remains patchy and limited in too many countries.

Community-led treatment education needs to be scaled up

We welcome the new “test and offer to treat” approach to ensure people living with HIV can benefit from starting treatment early. However, treatment initiation will always need to be guided by individual choices of patients who are knowledgeable about their options.  Unfortunately, such education is rarely supported at the moment. We urge the international community to ensure that adequate, community-led treatment education is an integral part of treatment scale up.

Middle income countries need affordable access to essential medicines

We welcome the recommendation in the guidelines for the use of new antiretroviral drugs such as dolutegravir, which is more potent, has fewer side effects and a lower risk of resistance for patients, than previous drugs. However, this drug will not be available for the vast majority of people who need it in middle income countries, because of patents and the drug’s exclusion from a voluntary license issued by ViiV Healthcare in 2014.

We urge ViiV to extend its license to all middle income countries currently excluded. We call on governments to use public health safeguards such as compulsory licenses, when needed, to ensure access to essential medicines.

Governments need to adopt and implement routine viral load monitoring now

While we are happy to see reaffirmation for routine viral load monitoring in the consolidated guidelines, we are dismayed that it is still not routinely available for people living with HIV in far too many countries. The campaign ‘Be Healthy – Know your viral load’ shows that viral load testing is not routinely available in the many African countries that adopted the 2013 WHO recommendations. Other countries, such as India, have still not adopted recommendations, and only recommend viral load tests following signs of treatment failure.

We urge governments to fast track the adoption of this recommendation, and ensure if there are costs to patients, that these are affordable. In the long term this will ensure better health outcomes for people living with HIV, and it will save lives and domestic resources.

“We urge national governments, the international community and the pharmaceutical industry to ensure HIV testing, and uninterrupted, quality HIV treatment is available to everybody,” explains Christine Stegling, Executive Director of ITPC. “Communities and individuals should be supported to understand the treatment options available to them. Furthermore effective medicines and diagnostics for testing and treatment should be accessible to everybody, including those most affected, such as sex workers, men who have sex with men, people who use drugs and adolescents, regardless of geographic location and income level of the country.”

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Accelerate Expansion of Antiretroviral Therapy to all people Living with HIV: WHO. 02/12/2015

Published at WHO


GENEVA– On World AIDS Day the World Health Organization (WHO) emphasizes that expanding  antiretroviral therapy to all people living with HIV is key to ending the AIDS epidemic within a generation.

“The Millennium Development Goal of reversing the HIV epidemic was reached ahead of the 2015 deadline - an incredible achievement that testifies to the power of national action and international solidarity," declared WHO Director General Margaret Chan. 

Expansion of antiretroviral therapy (ART) has resulted in a stark reduction of AIDS-related deaths. At the same time, increasingly effective prevention efforts have reduced  numbers of new HIV infections. Since the epidemic’s  peak in 2004, the number of - deaths has fallen by 42% with some 7.8 million lives being saved over the last 15 years, according to a new WHO report. The number of new infections has fallen by 35% since the turn of the century. 

Over the last 15 years, scale-up of ART has been most dramatic in the Africa Region where now more than 11 million people are receiving HIV treatment, up from 11 000 at the turn of the century.  People living with HIV in Africa are now more likely to receive treatment than people living in most other parts of the world. Globally, in June 2015 close to 16 million people out of a total of 37 million people living with HIV were taking ART. 

Doubling access to testing and antiretroviral therapy

At the UN General Assembly in September, world leaders endorsed a new set of Sustainable Development Goals and milestones, including a call for ending the AIDS epidemic by 2030. Reducing the number of new infections by 75% and doubling the number of people on ART by 2020 are the first milestones towards achieving this goal.  

Trial results published earlier this year have confirmed that people living with HIV who begin antiretroviral therapy soon after acquiring the virus – before the virus has weakened their immune systems - are more likely to stay healthy and less likely to transmit the virus to their partners. Those findings led WHO in September to recommend that everyone living with HIV be offered treatment.

In  the effort to help countries implement the “treat all” recommendation, WHO is now presenting  an additional set of recommendations on how to expand ART to all – in a rapid,  focused,  and efficient manner.  

These recommendations include using innovative testing approaches such as community or self-testing to help increase the number of people who know their HIV status; starting treatment faster in those people who are diagnosed with HIV;  bringing ART  to the community;  and allowing for greater intervals between clinic visits for people who have been stable on ART for some time. They also highlight the importance of improving  access to viral load testing and new classes of antiretroviral drugs. 

“WHO applauds governments, civil society, and organizations  that have made availability of life-saving antiretroviral therapy possible in the most trying circumstances. The new recommendation to

expand ART to all people living with HIV is a call to further step up the pace,” said Dr Winnie Mpanju-Shumbusho, Assistant Director General at WHO.

Preventing new infections 

Reducing the number of new HIV infections remains a major focus for the vision of ending AIDS. There is increasing concern about a slow down–or even reversal - in the decrease of new infections in some countries and among some of the most affected population groups. “We must deploy all means to strengthen the HIV prevention response. The health sector can and must play a central role,” added Dr Mpanju -Shumbusho

Already, over the last 5 years in Africa some 10 million men have undergone voluntary medical circumcision, a procedure that reduces their risk of acquiring HIV by 60%. New approaches to prevention are also emerging, including the use of antiretroviral drugs to help people at substantial risk from acquiring HIV. WHO now recommends this practice, called “pre-exposure prophylaxis,” or PrEP, as an additional option to augment comprehensive prevention for people at heightened risk of HIV infection. Other elements of this package include behaviour-change communication, the consistent use of male and female condoms and prevention programmes for key populations, including harm reduction for people who use drugs.

The same drugs that keep people living with HIV from becoming sick also prevent transmission of the virus from pregnant women to their infants. Among the 22 countries that account for 90% of new HIV infections, 8 have reduced new infections among children by more than 50% since 2009, based on 2013 data, and another 4 are close to that mark.

Ingredients of success

Some low- and middle-income countries have made remarkable progress towards universal access to  HIV services:  12 countries have ensured that 60% or more of all people living with HIV are aware of their infection and receiving antiretroviral therapy. Key ingredients of the successful HIV response in these countries are national ownership, greater focus of HIV services to reach the  most affected locations and populations based on good data, and simplification of prevention and treatment services.

“The sense of urgency that was the norm during the disease’s most-destructive years must not be allowed to abate,” Dr Mpanju-Shumbusho said. “HIV remains a major health challenge - drawing sharp attention to health system weaknesses and gaps in  universal health coverage.  Addressing these issues will be critical to meeting the new global targets for AIDS.”

 

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India and Africa Strengthen Partnership on accessible and Affordable Medicines. 02-11-2015

Published at UNAIDS

30 October 2015


During a high-level event on 30 October on the sidelines of the Third India-Africa Forum Summit 2015 in New Delhi, India, leaders from India, the African Union, several African nations and major Indian pharmaceutical companies pledged to address existing and emerging challenges to health commodity security in Africa.

The Indian pharmaceutical industry produces low-cost generic medicines that have been instrumental in scaling up access to HIV treatment in developing countries. The low price of generic first-line regimens is one of the factors that have contributed to the milestone achievement of providing access to life-saving antiretroviral therapy to more than 15 million people around the world.

Of the 36.9 million people living with HIV in 2014, around 25.8 million live in sub-Saharan Africa. By mid-2015, 11.4 million people living with HIV in sub-Saharan Africa had access to treatment. The achievement builds momentum for ending the AIDS epidemic as a public health threat by 2030.

However, despite the progress made so far, the price of second- and third-line medicines and diagnostics continues to be a barrier to HIV treatment access. One of the actions that will improve the situation is ensuring that pharmaceutical innovations are available, affordable and accessible to all.

As part of the Pharmaceutical Manufacturing Plan for Africa, African Union member states are taking steps to develop the local pharmaceutical sector on the African continent to enable Africa to manufacture a sustainable supply of high quality and affordable essential medicines. The development of the pharmaceutical industry will contribute to better public health outcomes and economic growth across the continent. An African and international consortium of partners that includes UNAIDS is supporting the local production of medicines.

Kenya, South Africa, Uganda and Zimbabwe are already producing World Health Organization pre-qualified antiretroviral medicines, with other countries planning to start production.

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New Report on HIV Treatment Launched for Parliamentarians. 21/10/2015

Published at UNAIDS

20 October 2015





UNAIDS and the Inter-Parliamentary Union (IPU) have published a best practice report to assist parliamentarians around the world frame policy and improve access to HIV treatment services.

Launching Fast-Tracking HIV treatment: Parliamentary action and policy options, the Executive Director of UNAIDS, Michel Sidibé, and the Secretary General of the IPU, Martin Chungong, described parliamentarians as having a pivotal role in expanding access to HIV treatment and helping UNAIDS reach its Fast-Track treatment targets.

They noted that expanding treatment involves respecting, protecting and promoting the rights of people most affected by HIV to ensure that everyone in need can access life-saving medicines. 

Quotes

"Parliamentarians play a key role in the AIDS response and increasing access to treatment. With their leadership, we can integrate science and policy to advance human rights and end the AIDS epidemic by 2030."

UNAIDS Executive Director, Michel Sidibé

"Where parliamentarians are effectively engaged in the AIDS response, they can provide the critical leadership for a new vision for health – health services that leave no one behind and make treatment a reality for all."

 

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HIV Positive People Should Start Treatment Immediately Says World Health Organisation. 05/10/2015

Published at Buzzfeed

Written by Patrick Strudwick

30 September 2015


 

The WHO, which will publish full guidelines later this year, says its recommendations could prevent 21 million deaths and 28 million new infections by 2030. Globally, if the WHO policy for early treatment was implemented it would increase the number of HIV-positive people on medication from 28 million to 37 million.

The new policy will increase pressure on the UK to offer preventative drugs to people at risk of infection.

The NHS is already broadly in line with the new WHO guidelines on treatment of those with HIV. But until July 2015, the NHS only recommended antiretroviral treatment for HIV-positive people whose immune systems had fallen below a certain level (a CD4 count – the chief measure of the immune system – of below 500).

NHS England issued new guidance in July allowing for a policy of “treatment as prevention” where antiretrovirals are given to HIV-positive patients to reduce onward infection. The medication lowers the virus to such low levels in the blood as to make it almost impossible to transmit the virus to someone else.

Last week, however, the British HIV Association (BHIVA), whose recommendations inform NHS policy, published guidelines recommending antiretroviral treatment “should be started, regardless of the CD4 count” not just to prevent onward infection but also for the health of the patient. This is in line with the new WHO advice.

Dr Duncan Churchill, a consultant in HIV and chair of BHIVA’s national treatment guidelines writing group, told BuzzFeed News: “Treatment guidelines are becoming congruent on this point, including, now, with WHO’s. Your relative risk of having a major opportunistic infection is significantly lower if you start antiretroviral therapy straightaway compared to if you defer until later.”

Justin Sullivan / Getty Images

However, the UK does not currently offer drugs as a preventative measure to those at risk of contracting HIV. This approach, known as PrEP (pre-exposure prophylaxis), uses the drug Truvada to protect HIV-negative people from infection.

The new WHO guidelines for the first time advise access to PrEP for all groups at risk of HIV infection – not only gay and bisexual men.

Churchill said that one of the reasons PrEP was not available on the NHS was cost.

“The difference between the NHS and WHO is around PrEP,” he said. “We haven’t yet produced guidelines on this issue but there is a process going on at the moment with NHS England considering this and it hasn’t concluded. PrEP has not yet been commissioned. The evidence is really good that in high-risk men who have sex with men (MSM) it works.

“My understanding is that the reason NHS England have not rushed into this is that they’re concerned about cost effectiveness in lower-risk people. That’s where the problem is – that in terms of cost it will balance and work in high-risk MSM groups but won’t balance in other groups in quite the same way.”


Around the world, policies for starting antiretroviral therapy (also called HAART, highly active antiretroviral therapy) vary considerably, along with significant differences in proportions of infected people having access to medication, and adhering to it.

In the US, for example, treatment is recommended as early as possible, but in some states as little as 29% of diagnosed HIV-positive people are receiving medication. In the UK it is around 90%, despite the recent contrast in policy over treatment.

PrEP has been approved for use among at-risk groups in the US since 2012 but remains inaccessible on the NHS, despite a succession of major studies showing its efficacy. This includes the PROUD study in the UK, which found PrEP reduces the risk of infection by 86%.

 

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START trial provides definitive evidence of the benefits of early HIV treatment. 07/08/2015

Published at AIDSmap
Written by Liz Highleyman
21 July 2015


Jens Lundgren at IAS 2015. Photo ©Steve Forrest/Workers' Photos/IAS
 

People who start antiretroviral therapy (ART) immediately after HIV diagnosis, while their CD4 cell count is still high, rather than waiting until it falls below 350 cells/mm3 have a significantly lower risk of illness and death, according to long-awaited findings from the START trial. The final study results were presented on Monday at the Eighth International AIDS Society Conference (IAS 2015) in Vancouver, Canada, and published simultaneously in the July 20 advance edition of the New England Journal of Medicine.

Professor Jens Lundgren of the University of Copenhagen reported that 1.8% of study participants in the immediate treatment group experienced a combined endpoint of serious AIDS-related events, serious non-AIDS events and death, compared with 4.1% in the deferred therapy group – a 57% reduction. The most common events in both arms were tuberculosis (TB) and cancer.

These findings suggest that HIV causes persistent immune system damage soon after infection, and "clearly indicate that ART should be provided for everyone regardless of CD4 count," Lundgren told aidsmap.com.

[The findings] "clearly indicate that ART should be provided for everyone regardless of CD4 count." Jens Lundgren

It is well known that starting ART before CD4 cell counts fall to low levels dramatically reduces the frequency of opportunistic illness and improves survival. A growing body of evidence shows that earlier treatment is associated with decreased disease progression and death, as well as minimising the risk of onward transmission of HIV.

But very early HIV treatment can have drawbacks, too, including longer exposure to potentially toxic therapy. In addition, some early treatment critics have expressed concern that people with HIV could be pressured to start treatment before they are ready, to benefit others rather than their own health

START design

Investigators with the INSIGHT START Study Group designed the Strategic Timing of Antiretroviral Treatment trial to shed more light on the optimal timing of HIV therapy, especially for people with CD4 cell counts in the normal range. The study began wide enrolment in March 2011.

START participants entered the trial with a CD4 count above 500 cells/mm3. They were randomly assigned to either start treatment immediately or to delay therapy until their CD4 count fell below 350 cells/mm3 or they developed symptoms of AIDS. They used a variety of antiretroviral regimens selected by study clinicians.

The study enrolled 4685 adults living with HIV in 35 countries worldwide, including just over half from low- and middle-income countries. Nearly three-quarters were men and the average age was 36 years. About 45% were white, 30% were black, 14% were Hispanic/Latino and 8% were Asian. Just over half were men who have sex with men.

At study entry, participants had been diagnosed with HIV for a median of one year and had never used ART. About a third each had CD4 counts between 500-600 and between 600-700 cells/mm3, with 11% having more than 900 cells/mm3. Pre-treatment HIV viral load was most often between 3000 and 30,000 copies/ml, but 10% had >100,000 copies/ml.

START primary results

The START Data Safety and Monitoring Board (DSMB) stopped the randomised portion of the trial ahead of schedule in May 2015 when it determined that there was enough evidence to show a significant benefit of immediate treatment. All remaining untreated participants were offered the option to start therapy. They will continue to be followed for long-term outcomes, and a set of sub-studies is looking at specific manifestations including neurological function, artery function, bone density and liver disease.

"The HIV research community needs to have solid evidence for making global recommendations on treatment..now we have evidence that aligns individual benefit and prevention benefit without harm." Jens Lundgren

At the time the study was halted, participants had been followed for an average of three years, accruing a total of 14,060 person-years of follow-up time. Most (94%) in the immediate arm were on still on treatment and 28% in the deferred arm had started. Retention in START was ‘excellent’ according the researchers, and adherence was good once treatment was initiated.

People in the deferred group started treatment in a median of three years – less than the predicted four years. Nearly a third started ART with a CD4 count of 250-350 cells/mm3, but 8% did not do so until they fell below 250 cells/mm3. The rest did so at higher levels than the trial's treatment-initiation threshold, including 8% who started with more than 750 cells/mm3. Over the course of follow-up, people in the deferred therapy group had CD4 counts that were 194 cells/mm3 lower, on average, than those who started treatment immediately.

Combined endpoint

Looking first at the combined primary endpoint of serious AIDS-related events, serious non-AIDS events or death, there were 42 of these events (1.8%, or 0.60 per 100 person-years [PY]) among people randomised to immediate treatment, compared to 96 events (4.1%; 1.38 per 100 PY) in the deferred treatment group, for a 57% lower risk (hazard ratio [HR] 0.43; 95% CI 0.30-0.62, p<0.001).

The researchers also analysed the endpoint components separately. Serious AIDS events included opportunistic infections and AIDS-defining cancers (cervical cancer, Kaposi’s sarcoma [KS] and certain types of lymphoma), while serious non-AIDS events included cardiovascular disease, end-stage kidney disease, decompensated liver disease and non-AIDS cancers (all other malignancies).

Serious AIDS events

There were 14 serious AIDS events (0.20 per 100 PY) in the immediate treatment group and 50 events (0.72 per 100 PY) in the deferred group, for a 72% risk reduction (HR 0.28; 95% CI 0.15-0.50, p<0.001). The difference in rates of AIDS events became apparent around 24 months and then continued to diverge, Lundgren reported.

Looking at the types of events, TB was the most common event in both the immediate and deferred treatment arms (6 vs 20 cases, respectively). Opportunistic conditions including lymphoma (3 vs 10 cases), KS (1 vs 11 cases) and Pneumocystis pneumonia (1 vs 5 cases) occurred much more often in the delayed treatment group. This was true even though most people who delayed treatment spent most of their time in the study with a CD4 count well above the traditional 'danger zone' below 200 or 350 cells/mm3.

Serious non-AIDS events

Turning to serious non-AIDS events – including deaths due to other non-AIDS causes – there were 29 events (0.42 per 100 PY) in the immediate group and 47 events (0.67 per 100 PY) in the deferred group, for a 39% risk reduction (HR 0.61; 95% CI 0.38-0.97, p = 0.04). Here, the curves for the occurrence of these events "did not split as quickly or markedly" as for AIDS events, Lundgren said.

The most frequent non-AIDS events were non-AIDS cancers (9 in the immediate vs 18 in the deferred group) and cardiovascular disease (12 vs 14 cases, respectively). Serious liver or kidney disease were rare in both arms (1 case in the immediate arm vs 2 in the deferred arm).

Deaths

Looking at overall deaths, there were 12 (0.17 per 100 PY) in the immediate group and 21 (0.30 per 100 PY) in the deferred group. However, this 42% reduction in risk was not statistically significant (HR 0.58; 95% CI 0.28-1.17, p = 0.13).

In both arms, the leading cause of death was accidents, violence or suicide (four in the immediate and six in the deferred arm). There was one death due to active HIV/AIDS in the immediate group compared with four in the deferred group. But other causes of death were scattered between the two groups with very small numbers and "no clear pattern", according to Lundgren.

Cancer and cardiovascular disease

Focusing on cancer, there were 14 cases of any type (0.20 per 100 PY) in the immediate treatment group and 39 cases (0.56 per 100 PY) in the deferred group, a 64% risk reduction that was significant (HR 0.36; 95% CI 0.19-0.6, p = 0.001). This difference became apparent after 12-16 months and from then on there was a clear separation, Lundgren said.

AIDS-defining malignancies KS (1 vs 11 cases) and lymphoma (3 vs 10 cases) were much more frequent in the deferred treatment group. But for other cancer types the numbers were small and there were no notable differences. This was true for both cancers caused by infectious agents – such as human papillomavirus (HPV) for anal and cervical cancer – and for those with no known infectious cause.

Serious cardiovascular events occurred with similar frequency in the immediate and deferred groups (12 vs 14 cases). There were three cardiovascular deaths in the early ART arm compared with one in the delayed group, but these numbers are too small to draw conclusions. At any rate, Lundgren said, there is no evidence from this study to demonstrate any benefits of early treatment for cardiovascular disease, but this also cannot be ruled out.

Adverse events

Finally, the researchers looked at adverse events in the study, assessed in both ART-treated and untreated participants. Separately, rates of serious (grade 4) adverse events, unscheduled hospitalisations and deaths from any cause did not differ significantly in the immediate and deferred ART arms. However, when these events were combined there was a significant advantage in the early treatment group (HR 0.82; p = 0.01). The only specific adverse event with a notable difference was bacterial infections, which were significantly more common in the delayed treatment arm.

Despite the long-standing concerns about early ART leading to added side-effects, Lundgren said there was "no apparent increased toxicity", seen in this study.

Implications of START

START participants who started immediate treatment saw similar benefits regardless of sex, age, race/ethnicity or geographic region. Importantly, the benefits of early ART were comparable in wealthy and low- or middle-income countries.

However, the study team acknowledged that START participants were younger than expected and experienced fewer overall events than originally predicted. Further research is needed on complications among people ageing with HIV.

As noted, most people in both the immediate and deferred treatment arms spent most of their time in the study with a CD4 count over 500 cells/mm3, and more than two thirds of the AIDS and non-AIDS events occurred at this level.

Based on these findings, Lundgren suggested that we cannot rely on CD4 count to fully capture immune deficiencies in early HIV infection. "This trial demonstrates that even in people with high CD4s, there's a hole in the immune system if you're HIV-positive," he explained. ART is able to fill those gaps at least partially, but even fully suppresses therapy may not be able to completely reverse immune damage once it's done. Lundgren added that it will be important to develop new types of treatment beyond antiretrovirals aimed at restoring lost immune function.

When the START DSMB halted the trial prematurely, the early findings were provided to the World Health Organization (WHO) panel working on updated global HIV treatment guidelines. WHO announced this week that its forthcoming guidelines will recommend treatment for all, regardless of CD4 count. US guidelines adopted universal HIV treatment in 2013 and the British HIV Association did so in its new draft guidelines, issued in June after the release of the preliminary START findings.

"The HIV research community needs to have solid evidence for making global recommendations on treatment," Lundgren told aidsmap.com. "We want to build an evidence base and not rush it. But now we have evidence that aligns individual benefit and prevention benefit without harm. I'm very happy we were able to provide that evidence and that WHO is responding."

"IAS 2015 will be remembered as the definitive moment when the world agreed earlier initiation of treatment is the best way to preserve the health of people living with HIV, and one of the best tools we have to slow HIV transmission to others," said conference co-chair Julio Montaner of the British Columbia Centre for Excellence in HIV/AIDS. "The new data presented today will inform HIV treatment guidelines worldwide, and inspire governments, funders and health systems to act to save millions more lives."

"We have to translate these findings into programs as quickly as possible," concurred US Global AIDS Coordinator Deborah Birx, speaking on a panel about START's implications after Lundgren presented the findings. "All of us have a moral obligation now."

 

 

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WHO Guidelines to Recommend HIV Treatment for All. 07/08/2015

Published at POZ
21 July 2015


The World Health Organization’s upcoming HIV treatment guidelines will recommend HIV meds for everyone living with the virus regardless of their CD4 count, aidsmap reports.

The WHO’s new guidelines will come out later this year and will update the current 2013 version. Meg Doherty, MD, PhD, of the WHO Department of HIV/AIDS made the announcement on Sunday via a satellite meeting before the 8th International AIDS Society Conference (IAS 2015) in Vancouver, British Columbia.

The recommendations arrive on the heels of data from the START and TEMPRANO studies; both found many benefits to starting treatment when CD4 counts remain above 500.

According to aidsmap, the new WHO guidelines recommend:
Treatment for all adults and adolescents regardless of CD4 count, prioritizing those with CD4 counts below 350 cells/mm3 and those with AIDS-defining illnesses.

  • Treatment for all children.
  • Treatment for all pregnant women, leading to lifelong treatment.
  • Pre-Exposure Prophylaxis (PrEP) should be offered as an additional prevention choice for people at substantial risk of HIV infection.

 

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GroundUp: Two massive medicine trials will change the way HIV is treated 07/08/2015

Published at Daily Mavareck
Written by Nathan Geffen
23 July 2015


GroundUp-aidsnathangeffenSUBBED.jpg

The The results of two large medicine trials, known as Strategic Timing of Antiretroviral Treatment (Start) and Temprano, published this week show that the health of people with HIV will benefit from starting antiretroviral treatment earlier. These findings are a climax of a bit more than three decades of research on this relatively new disease.
 
The Start trial results were presented at the International AIDS Conference in Vancouver on Monday. The trial is mostly funded by the US government. It compared early versus delayed treatment in over 4,600 people with HIV. The trial participants were generally healthy and in the early stages of HIV infection. Just over 4% of participants on delayed treatment became ill or died versus just under 2% on the immediate arm, meaning that early treatment reduced the risk by half. The trial, which began in 2009, was only expected to have a result by the end of 2016, but a board responsible for monitoring the safety of the trial noticed in May that the difference between the immediate and deferred participants had become larger than could be explained by chance. Therefore everyone on the deferred arm is now being offered treatment.
 
The implication is that antiretroviral treatment should be recommended when people are diagnosed with HIV or shortly thereafter. Anyone already diagnosed with HIV should consider starting treatment. The study researchers tried to identify patients who would be more likely to benefit from early treatment. But neither sex, nor race, nor whether they smoked, nor what part of the world they lived in, nor heart health, nor income, nor several other measures, gave any indication of who would especially benefit from starting treatment early. The diseases that early treatment protected most against were tuberculosis (TB), which was mainly seen in study participants in Africa, and cancer, which was mainly seen in study participants in Australia, Europe, Israel, and the US.
 
While Start was run in 215 clinics in 35 countries, the Temprano trial was run in nine care centres in Abidjan, Côte d’Ivoire. This trial, funded by the French government, was primarily concerned with whether early antiretroviral treatment reduced the risk of TB in people with HIV. It also looked at whether taking a six-month course of an anti-TB drug, isoniazid reduced the risk of getting TB. This study was also large - over 2,000 participants. And it too found that going onto antiretroviral treatment earlier reduced the risk of severe illness. So did taking isoniazid.
 
Compelling results
These trials have important implications for people with HIV worldwide. Treatment guidelines have differed across countries for some time because of different views on when to start, but now the evidence is clear. On Tuesday the Treatment Action Campaign (TAC) called for treatment to be recommended to everyone with HIV. Currently, the South African guidelines provide for treatment when a person with HIV’s CD4 count falls to 500 cells per cubic millimetre. This is likely to change soon.
 
It has been clear since a large trial called HPTN 052 was published in 2011 that if people with HIV undergo antiretroviral therapy they are much less likely to transmit the virus to their sexual partners. But it was not known if the risks of resistance and problems with adherence and drug toxicity outweighed the clinical benefits of starting early. With the publication of the Start and Temprano trials, we now have unequivocal evidence that the benefits of early treatment outweigh the risks. This is good news all round because it means the goal of reducing the number of new HIV infections is entirely consistent with the best treatment for patients. There are still challenges ahead though for the successful implementation of early treatment. Participants in Start had access to the best antiretroviral regimens. They also had a consistent drug supply and good care. Whether these factors will be sufficiently present in health facilities across sub-Saharan Africa, including South Africa, remains to be seen. Also, at rural clinics where there are capacity problems, patients with more advanced HIV infection will likely be prioritised to receive antiretroviral treatment. There will also be concerns about the cost of providing treatment for millions more people across the world, but these might be offset by the reduction in new HIV infections as a result of antiretroviral treatment, as well as fewer illnesses in people with HIV.
 
TB and HIV
Isoniazid to prevent TB in people with HIV is not widely used in South Africa. There have been technical questions about it that have concerned nurses and activists (including this writer). But the Temprano results are compelling and hopefully isoniazid prevention will become much more widely used.
 
HIV and TB are by far the biggest causes of ill health and death in South Africa, especially in young adults. More than 3-million South Africans have died of AIDS. About 6-million live with HIV, and, according to Department of Health statistics, more than 3-million people are on antiretroviral treatment.
 

In general, reports on treatment breakthroughs need to be treated with scepticism. Earlier this month, scientists at the University of Cape Town claimed that Vitamin D might slow HIV progression. A media article this week reports that “Rooibos, honeybush and garlic may protect against cancer”. These irresponsible claims are made based on the flimsiest of evidence. The Start and Temprano trials are in a different league. They represent the best of medical science: large publicly funded clinical trials that answer questions of immense importance.

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HIV: UN meets goal to treat 15 million. 15/07/2015

Published at BBC News
Written by Michelle Roberts
14 July 2015


 Drawing blood

The goal to get HIV treatment to 15 million people by the end of 2015 has already been met, says the United Nations Aids agency.

The landmark figure was reached in March - nine months ahead of schedule.

It follows decades of global efforts and investment to get antiretroviral drugs to those in need - such as people living in sub-Saharan Africa.

In 2000, when the UN first set goals to combat HIV, fewer than 700,000 people were receiving these vital medicines.

According to UN Aids, which has a report out today, the global response to HIV has averted 30 million new HIV infections and nearly eight million Aids-related deaths since the millennium.

Over the same time frame, new HIV infections have fallen from 2.6 million per year to 1.8 million, and Aids-related deaths have gone down from 1.6 million to 1.2 million.

Meanwhile, global investment in HIV has gone up from £3.1bn ($4.8bn) in 2000 to more than £13bn ($20bn) in 2014.

And concerted action over the next five years could end the Aids epidemic by 2030, says UN Aids.

But progress has been slower in some areas.

Ending Aids

A major gap seems to be in awareness of HIV status, which is the biggest barrier to treatment access, says the report.

And treatment access for children has lagged behind adults - although this is now improving.

The proportion of children living with HIV who receive antiretroviral therapy almost doubled between 2010 and 2014 (from 14% to 32%), but coverage "remains notably lower than it does for adults", says the report.

Even though new HIV infections have gone down, there is still an unacceptable number of new HIV infections each year, contributing to the burden of the epidemic.

In 2014, sub-Saharan Africa accounted for 66% of all new HIV infections. And at the last headcount, there were an estimated 25.8 million people in this region living with HIV. The estimated count for the whole world was 36.9 million.

This year sees the switch from Millennium Development Goals to broader Sustainable Development Goals.

Ban Ki-moon, Secretary General of the United Nations said: "The world has delivered on halting and reversing the Aids epidemic.

"Now we must commit to ending the Aids epidemic as part of the Sustainable Development Goals."

The report says the next five years will be critical and recommends front-loading investment to "sprint" towards an ambition of ending the Aids epidemic by 2030.

 

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Community-based adherence clubs show high retention in HIV care and treatment adherence. 14/07/2015

Published at AIDSmap
Written by Lesley Odendal
10 July 2015


People with HIV who were receiving their HIV treatment outside of health facilities in community-based ART adherence clubs close to or in a patient’s home demonstrated extremely high rates of retention in care and adherence to treatment, according to a study presented at the 7th South African AIDS Conference last month in Durban. The study was presented by Suhair Solomon from Médicins Sans Frontières (MSF/Doctors Without Borders) and conducted in Khayelitsha, a large informal settlement of 500,000 people, situated 40km outside of Cape Town in South Africa.

196 of 203 people (97%) who were enrolled in the community clubs were retained in ART care. Loss to follow-up was defined as no recorded clinic or club visit for more than three months.

The community-based adherence clubs are based on the same model as the out-of-clinic adherence club for delivery of care instituted at Khayelitsha’s Ubuntu clinic, which has shown better retention of care than standardised health facility based care.   To date, the Cape Town Metro has more than 400 of these clubs as part of a partnership between MSF, the Western Cape Department of Health, Cape Town’s City Health and the Institute for Healthcare Improvement.

However, instead of holding club meetings near the health facility, the club members choose a venue close to their homes, or host the club within their own homes. In this way, group members are from the same geographical area and do not need to pay for transport costs.

Of the 196 people retained in ART care, 172 (88%) remained in club care, while 22 (11%) received their ART at the clinic and 2 (1%) were transferred. 95% of community club care members (145 of 153 due for viral load testing) were virally suppressed.

Of those with 12 months follow-up in community clubs (n=101), 99% (n=100) remained in ART care. Of the 98 due for viral load testing, 96% (n=89) had at least one viral load test done, of which all were virally suppressed.

The median time on ART was 3.6 years (IQR: 2.2 – 5.5 years) and the median time in community clubs was 336 days (IQR: 224 – 728). 158 (78%) of those enrolled in community clubs are female. The median age at enrolment was 36.7 years (IQR: 32.7 – 42.8).

In the adherence club model, groups of 15 to 30 people are formed and convene every two months in meetings facilitated by non-clinical staff. However, the community club size ranged from 10 to 38 members, due to club members wanting to belong to a club that is closest to their homes.

All club members are stable patients who have been on ART for more than 12 months, with two consecutive suppressed viral load tests, who have no health conditions that require frequent clinic consultation. A clear clinical referral pathway for clinical support is mapped out at the establishment of the club.

Essential tasks, such as weight measurement and symptom-based general health assessment, are conducted by a trained lay health worker counsellor (the club facilitator). Medicines are pre-packaged for each participant and brought to the group by the facilitator. Anyone reporting symptoms suggestive of illness, adverse drug effects or weight loss is referred back to the clinic to be assessed by a nurse.

People enrolled in the club also have the option of using a ‘treatment buddy’ to collect their medication when they are unable to. 61% (n=124) had used a buddy for pick up at least once, while 25% (n=50) had used a buddy more than once.

The aim of the programme is to relieve the burden on formal health services, promote adherence through peer support, reduce waiting times for patients and to identify defaulters early.

“Homes and community venues close to a patient’s home are feasible options for the delivery of ART, with high retention rates. It empowers patients through self-management and reduces community stigma. This model should be considered for roll-out in other settings,” said Solomon.

It is however cautioned that this requires resource management and planning, including a reliable drug supply, suitable monitoring systems, trained and supported lay healthcare workers, effective referral systems and adequate funding.

Family ART clubs

MSF also supports the implementation of family ART adherence clubs which are a long term retention model of care catering for children stable on ART and their caregivers, which follows a similar lay counsellor run model as the community-based clubs. The family clubs are supported by nurses, who write pharmacy prescriptions for children under 40kg, based on a quick weight assessment.

Between March 2011 and September 2013, 146 children on ART and their caregivers enrolled in family clubs. Overall 136 (93%) children were retained in care, 96 (66%) in family club care, 33 (23%) in clinic care, 7 (5%) transferred out and 10 (7%) were lost to follow up. Of those retained in family club care, 91 (95%) had suppressed viral loads in the last 12 months.

Of the children retained in family club care, all of those between 7 and 10 years of age achieved partial disclosure. This is when a child is told some information about their health and why they take medication, but the word HIV is not used. 57 (79%) children over the age of 10 years achieved full disclosure.

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Starting Antiretroviral Treatment Early Improves Outcomes for HIV-Infected Individuals. 3/6/2015

Published at NIAID
Written by National Institute of Allergy and Infectious Diseases (NIAID)
27 May 2015


NIH-Funded Trial Results Likely Will Impact Global Treatment Guidelines

A major international randomized clinical trial has found that HIV-infected individuals have a considerably lower risk of developing AIDS or other serious illnesses if they start taking antiretroviral drugs sooner, when their CD4+ T-cell count—a key measure of immune system health—is higher, instead of waiting until the CD4+ cell count drops to lower levels. Together with data from previous studies showing that antiretroviral treatment reduced the risk of HIV transmission to uninfected sexual partners, these findings support offering treatment to everyone with HIV.

The new finding is from the Strategic Timing of AntiRetroviral Treatment (START) study, the first large-scale randomized clinical trial to establish that earlier antiretroviral treatment benefits all HIV-infected individuals. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, provided primary funding for the START trial. Though the study was expected to conclude at the end of 2016, an interim review of the study data by an independent data and safety monitoring board (DSMB) recommended that results be released early.

“We now have clear-cut proof that it is of significantly greater health benefit to an HIV-infected person to start antiretroviral therapy sooner rather than later,” said NIAID Director Anthony S. Fauci, M.D. “Moreover, early therapy conveys a double benefit, not only improving the health of individuals but at the same time, by lowering their viral load, reducing the risk they will transmit HIV to others. These findings have global implications for the treatment of HIV.”

“This is an important milestone in HIV research,” said Jens Lundgren, M.D., of the University of Copenhagen and one of the co-chairs of the START study. “We now have strong evidence that early treatment is beneficial to the HIV-positive person. These results support treating everyone irrespective of CD4+ T-cell count.”

The START study, which opened widely in March 2011, was conducted by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) at 215 sites in 35 countries. The trial enrolled 4,685 HIV-infected men and women ages 18 and older, with a median age of 36. Participants had never taken antiretroviral therapy and were enrolled with CD4+ cell counts in the normal range—above 500 cells per cubic millimeter (cells/mm3). Approximately half of the study participants were randomized to initiate antiretroviral treatment immediately (early treatment), and the other half were randomized to defer treatment until their CD4+ cell count declined to 350 cells/mm3. On average, participants in the study were followed for three years.

The study measured a combination of outcomes that included serious AIDS events (such as AIDS-related cancer), serious non-AIDS events (major cardiovascular, renal and liver disease and cancer), and death. Based on data from March 2015, the DSMB found 41 instances of AIDS, serious non-AIDS events or death among those enrolled in the study’s early treatment group compared to 86 events in the deferred treatment group. The DSMB’s interim analysis found risk of developing serious illness or death was reduced by 53 percent among those in the early treatment group, compared to those in the deferred group.

Rates of serious AIDS-related events and serious non-AIDS-related events were both lower in the early treatment group than the deferred treatment group. The risk reduction was more pronounced for the AIDS-related events. Findings were consistent across geographic regions, and the benefits of early treatment were similar for participants from low- and middle-income countries and participants from high-income countries.

“The study was rigorous and the results are clear,” said INSIGHT principal investigator James D. Neaton, Ph.D., a professor of biostatistics at the University of Minnesota, Minneapolis. “The definitive findings from a randomized trial like START are likely to influence how care is delivered to millions of HIV-positive individuals around the world.” The University of Minnesota served as the trial’s regulatory sponsor and statistical and data management center.

Prior to the START trial, there was no randomized controlled trial evidence to guide initiating treatment for individuals with higher CD4+ cell counts. Previous evidence to support early treatment among HIV-positive people with CD4+ cell counts above 350 was limited to data from non-randomized trials or observational cohort studies, and on expert opinion.

START is the first large-scale randomized clinical trial to offer concrete scientific evidence to support the current U.S. HIV treatment guidelines, which recommend that all asymptomatic HIV-infected individuals take antiretrovirals, regardless of CD4+ cell count. Current World Health Organization HIV treatment guidelines recommend that HIV-infected individuals begin antiretroviral therapy when CD4+ cell counts fall to 500 cells/mm3 or less.

In light of the DSMB findings, study investigators are informing all participants of the interim results. Participants will be offered treatment if they are not already on antiretroviral therapy, and they will continue to be followed through 2016.

The HIV medicines used in the trial are approved medications donated by AbbVie, Inc., Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, LLC, and Merck Sharp & Dohme Corp.

In addition to NIAID, funding for the START trial came from other NIH entities, including the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Mental Health; the National Institute of Neurological Disorders and Stroke; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the NIH Clinical Center; and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Funding was also provided by the National Agency for Research on AIDS and Viral Hepatitis (ANRS) in France, the Federal Ministry of Education and Research in Germany, the European AIDS Treatment Network and government organizations based in Australia, Denmark, and the United Kingdom.

The Medical Research Council Clinical Trials Unit at University College London; the Copenhagen HIV Program at the Rigshospitalet, University of Copenhagen in Denmark; the Kirby Institute at the University of New South Wales in Sydney, Australia; and the Veterans Affairs Medical Center affiliated with George Washington University in Washington, D.C. coordinated the work of the 215 START sites.

For more information about the START trial, see the Questions and Answers or visit ClinicalTrials.gov using study identifier NCT00867048.
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Treating H.I.V. Patients Before They Get Sick. 2/6/2015

Published by NY times
30 May 2015


 A major international clinical trial has provided the strongest evidence yet that people infected with H.I.V., the virus that causes AIDS, should get treated as soon as possible, even if they are feeling well, to ward off serious illness and fatal complications in future years. The finding raises the powerful moral question of whether global and national organizations can find the will — and the resources — to protect millions of people from deaths and diseases that could be prevented.

The study was conducted in 35 countries and designed to end the debate about when to start treatment. The randomized trial enrolled 4,685 men and women who were infected with H.I.V. and whose CD4 cell counts, a measure of immune system strength, were still normal. About half of them were started on treatment with antiretroviral drugs immediately. The other half were given treatment only after their counts fell to a worrisome level.

The results were striking. After being followed for an average of three years, those in the immediate-treatment group were 53 percent less likely to die or develop AIDS or other serious illnesses than those in the deferred-treatment group. There were 86 such events among those with deferred treatment but only 41 in the early-treatment group.

Based on these results and previous studies that were smaller or more limited, the National Institute of Allergy and Infectious Diseases, the primary funder of the study, recommended offering treatment to everyone infected with H.I.V. Currently, fewer than 14 million of the estimated 35 million people in the world infected with H.I.V. are taking antiretroviral drugs. Treating all the infected people in the world’s poor and middle-income countries immediately would cost almost $20 billion, roughly triple the current expenditures.


A woman in New Delhi with her antiretroviral drugs.

Andrew Caballero-Reynolds / Agence France-Presse — Getty Images

While costly, putting all H.I.V.-infected people on the drug regimen would provide a double benefit. It would improve the health of those infected and, by suppressing the amount of virus in their bodies, lessen the risk that they might spread the virus to others, through unprotected sex or through needle-sharing among drug addicts.

In the United States, current guidelines recommend that all H.I.V.-infected people take antiretrovirals regardless of their CD4 counts. San Francisco has been recommending immediate treatment since 2010, and new infections in that city have dropped substantially since then. New York City has been urging immediate treatment since 2011 but has not yet seen the same sharp decline in new cases. Nationally, only about 450,000 of the estimated 1.2 million people infected with H.I.V. are undergoing treatment.

A committee of the World Health Organization is planning to issue new treatment guidelines soon. It has good reason to recommend treatment for all infected people, even those with normal CD4 counts.

 

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Drugs to keep people with HIV alive should be given without delay, trial finds. 1/6/2015

Published at The Guardian
Written by Sarah Boseley
27 May 2015


Scientists find that antiretroviral treatment should be administered before HIV virus has weakened the immune system.

An electron microscope image of an H9 T cell infected with HIV.

 

 

 

  

 

An electron microscope image of an H9 T cell infected with HIV. The Start (Strategic Timing of AntiRetroviral Treatment) trial has found that drugs to keep people with HIV alive should be given as early as possible. Photograph: AP

 

Drugs to keep people with HIV alive should be given as early as possible – before the virus has weakened their immune system – and not delayed as they are now, according to scientists involved in a major trial.

The Start (Strategic Timing of AntiRetroviral Treatment) trial was stopped because of overwhelming evidence that people with HIV did better if they were put on antiretroviral treatment when their CD4 count (a measure of how well their immune system is functioning) was above 500 rather than 350, as guidelines currently advise in the UK and many other countries.

Anthony S Fauci, director of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health which funded the trial of more than 4,600 people, said it was stopped because it became clear that early treatment cut the number of people who died or suffered serious Aids-related illness in half. The trial should have ended in 2016. Those whose treatment was being delayed will now get the drugs immediately.

“These findings clearly demonstrate that starting antiretrovirals sooner rather than later is of considerable benefit to the HIV-infected individual,” Fauci said.

The results are likely to change the way people with HIV are treated all over the world. In both high- and low-income countries, the results were the same: a 53% drop in serious illness and death in those given drugs while their immune systems were more robust.

“I would be surprised if guidelines committees didn’t very seriously look at this and bring it into their calculations,” said Fauci. “[In the US,] if you are infected, you get treated.” That has been based on expert opinion, without evidence from a randomised trial, which is why Start was launched. But in the UK and other countries including most of Europe, treatment is deferred.

There would be financial implications, Fauci acknowledged. “This is going to cost money if you have to go out and treat everyone who is infected,” he said. It would be another motivation for getting resources into programmes such as the Global Fund and Pepfar (the US president’s emergency plan for Aids relief), which provide money for treatment in the poorest countries.

But treating early would be cost-effective, because those who are treated early will not suffer severe illnesses as a result of HIV. “There is no doubt that it is going to be less expensive to treat people early,” he said.

British experts hope that Nice (the National Institute for Health and Care Excellence) will now recommend that anyone with HIV is given the drugs at diagnosis. That would have the great additional benefit of reducing transmission, since it has been shown in gay men that the drugs suppress the virus to the point where people are no longer infectious.

Prof Ab Babiker of the Medical Research Council clinical trials unit at UCL, one of the trial coordinators, said: “We know from previous trials that ART (antiretroviral therapy) reduces the risk of transmission of HIV. The findings from Start clearly demonstrate that early treatment is also of benefit to the individual. This provides a very strong rationale for offering treatment to all HIV-positive individuals as soon as they are diagnosed.”

Dr Alejandro Arenas-Pinto from UCL, the trial’s chief investigator for the UK, said: “Early ART initiation has been advocated by some investigators in the past, but it is the Start trial that provides strong evidence to support the strategy based not only on clinical benefit but also on lack of harm for the individual. The discussion between patients and clinicians on when to start ART would, from now on, be evidence-based.”

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How South Africa can stop HIV drug resistance in its tracks. 26/05/2015.

Published at The Conversation
Written by Imogen Wright
22 May 2015


 

If patients contract drug resistant HIV, they may have to be prescribed more expensive drugs. Finbarr O'Reilly/Reuters

Health care is entering a new era of personalised medicine, where treatment is tailored to the individual patient. To usher in this era, researchers across the world are trying to create cheaper tests that can find DNA mutations in humans, bacteria and viruses.

In South Africa, researchers are using these new, high-throughput testing methods to crack the problem of HIV drug resistance. Drug resistance testing is considered a critical part of an effective HIV treatment programme, but until now testing has been very costly.

Now, novel research in South Africa has come up with a solution that cuts the cost up to tenfold, raising the possibility of an HIV drug resistance test that could be accessible to almost anyone.

More than 30 years after its discovery, HIV continues to present an exceptional medical and public health challenge. Although anti-retroviral drugs (ARVs) are effective at disrupting the virus’s life cycle, the way HIV replicates is very unstable. Mutations creep into the virus’s DNA as it replicates, which can make the virus resistant to ARVs.

Drug resistance on the rise

HIV drug resistance could become a ticking time bomb for public health if resistant strains continue to spread. Patients with resistance to cheaper first-line anti-retrovirals must take more expensive alternatives, which both limits their options and vastly increases the costs of treatment.

The World Health Organization estimates that in 2010 one in 20 HIV-positive patients worldwide was infected with a drug-resistant strain. Later studies suggest this figure is rising in low- and middle-income countries.

In South Africa, over 6.4 million people are infected with HIV. Of these, 2.5 million are taking anti-retrovirals. There are 18 different drugs available in the country and patients are usually prescribed three or more drugs concurrently to lessen the chances of resistance.

Around nine percent of patients are failing first-line anti-retroviral therapy year-on-year in South Africa. If a patient fails treatment because of resistance to their prescribed anti-retrovirals, the resistant virus is free to replicate unchecked. If this resistance is not picked up and treated, the virus will destroy the patient’s immune system and speed the progression to AIDS.

Patients who have developed drug resistance are also more infectious than those on a fully effective treatment regimen. There is more virus in their bodily fluids, which means that there is a higher chance they will infect someone else. To make matters worse, the newly-infected person may contract the resistant strain.

Preventing the time bomb

Most public health guidelines recommend a drug resistance test when an HIV-positive patient is diagnosed, and another drug resistance test when a patient’s treatment fails.

A drug resistance test works by ‘reading’ the DNA of the HIV in a sample of a patient’s blood (called sequencing), and checking it against a known list of drug-resistant mutations.

The South African HIV Clinicians Society currently recommends a test only when first-line anti-retroviral therapy has failed. However, fulfilling even this recommendation in practise is a significant challenge. Commercially available tests cost around R5000 per patient, which is an expensive burden on the South African public health sector.

New solutions

New technology, however, has the potential to lessen this burden. Our novel research at the university’s South African National Bioinformatics Institute reduces this cost up to tenfold, making an HIV drug resistance test accessible to almost anyone.

We have developed a web application that analyses HIV samples from many patients, which were sequenced concurrently using a high-throughput sequencing machine. Sequencing in parallel like this significantly reduces the per-patient cost.

High-throughput sequencing machines produce up to several million short, error-prone ‘reads’ of DNA sequences, which must be identified and corrected before they can be used to reconstruct a picture of the HIV in each patient’s blood.

Although this data is much more complex, our process can return results that are not only cheaper but also more accurate than the conventional, expensive approach. More copies of each patient’s HIV can be sequenced, which means it is more likely that drug-resistant mutations will be detected.

The software combines cloud computing with novel algorithms that correct errors in the data and accurately detect drug resistance mutations. The application then returns a simple traffic light report that indicates the drugs to which a patient is resistant (red), or susceptible (green). This report can be interpreted by a primary care physician and used to tailor a treatment regimen to a patient’s drug resistance profile.

This approach to drug resistance testing is inexpensive enough to be included as a routine part of HIV treatment in low-resource settings. It will not only improve individual patient outcomes, but also reduce the public health burden of new infections and transmitted drug resistance.

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Could a new HIV/AIDS vaccine boost the effects of antiretroviral therapy?. 6/5/2015

Published at BioMed Central
Written by Barbara Ensoli
29 April 2015


Research published in Retrovirology reports the results of a clinical trial that shows a new vaccine can boost an HIV-infected patient’s immune system and increase the effectiveness of anti-retroviral drugs. In this blog, co-author Barbara Ensoli talks about the benefits this new vaccine could bring to HIV patient care.

Needle syringe with a vaccine bottle. Credit NIH

Antiretroviral therapy (ART) is plagued by serious therapeutic failures. In HIV patients undergoing combined ART (cART), these include failure to fully restore the normal functioning of the immune system, and failure to eradicate the virus from cART-resistant reservoirs, leading to persistent virus reactivation and chronic immune activation.

These failures result in the development of the so-called non-AIDS-related diseases, leading to a higher risk of hospitalization and death. Moreover, non-adherence in taking antiretroviral medication everyday is widespread. In fact, for ART to be effective in controlling HIV, patients must take ART pills every day at least 95% of the time.

In real life, however, adherence is about 70%, everywhere, including North America and Europe. This is insufficient to block virus multiplication and transmission, continued damage to the immune system, progression to AIDS, development of drug resistance, and a 3.8 times increased risk of death. The cost of non-adherence for public health is huge: new infections, increased hospitalization costs and a need to use more expensive therapies due to drug resistance.

In our paper we report the first evidence of cART intensification by a HIV/AIDS vaccine, the Tat vaccine. Immunization with the Tat vaccine of 168 ART-treated volunteers, in a phase II study in Italy, led to restoration of the immune system well beyond that provided by ART. This suggests a protective role for anti-Tat antibodies against HIV-1 Tat, a key HIV virulence factor, which is critical in the virus life cycle, cell-to-cell virus transmission and disease progression.

These results are being confirmed by a 48-week trial of ART-intensification in 200 subjects in South Africa. Of note, unlike all the other HIV-1 proteins, Tat is infrequently targeted by specific antibodies in the course of the natural infection, and when this occurs the infection does not progress or it does so at a very slow pace.

This strongly supports the notion that anti-Tat antibodies exert a protective role against progression to disease. Strikingly, the Tat vaccine also significantly reduced the HIV-1 proviral DNA load, which is the latent form of the virus that accumulates in reservoirs. The results indicate that, three years after the first immunization, CD4+ T cells continue to increase and proviral HIV DNA continues to decrease.

The implications of a new HIV/AIDS vaccine

The trial results indicate that the Tat vaccine induces remarkable and durable changes consistent with a restoration of the immune system well beyond that provided by cART. In the end, the vaccinees were persons who had been on cART since six years on average and who had responded very well to therapy, a group in which you really don’t expect to see much beyond what the therapy has already done.

The changes induced by this vaccine clearly indicate that the Tat protein must play a very important role in the chronic infection in patients on effective cART, contributing to the residual disease and complications observed in these subjects despite the good response to therapy. Indeed, although unexpected, the proviral DNA reduction in the peripheral blood further confirms the key role of Tat in AIDS pathogenesis, including virus activation (even under cART), cell-to-cell virus transmission and immune cell dysregulation, which are critical for the establishment and replenishment of the virus reservoir. Proviral DNA reduction was progressive and durable.

We prove for the first time that cART may be intensified by therapeutic immunization and that proviral DNA load may be progressively lowered. These results provide evidence that the goal of a functional cure may be feasible.

The future of vaccine clinical trials

These results open new scenarios to investigate, namely whether this vaccine may help with virus control where patients have low adherence to cART, simplify or interrupt therapy, or even block progression to disease in asymptomatic subjects as suggested by studies in natural infection. To these aims phase III clinical trials are being planned in South Africa for implementation in the near future.

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Single-tablet regimens like Atripla no better than multiple tablets. 4/5/2015

Published at AIDSmap
29 April 2015


A new analysis has put in question the value to the NHS of treatments such as Atripla, Stribild and Eviplera which combine three or more antiretroviral drugs into a single tablet. While these treatments all have excellent outcomes, they can be five times more expensive than regimens made up of multiple tablets and non-branded drugs.

As clinical outcomes are just as good with some less expensive alternatives, some doctors believe that NHS spending on single-tablet regimens cannot be justified. They acknowledge that many people living with HIV prefer single tablets and find them more convenient. However, doctors are under pressure to keep their budgets under control without reducing the quality of care.

Single-tablet regimens are more expensive because they are patented, branded products, rather than generic medicines. When a new drug is produced, it is protected by patent, which means that the pharmaceutical company which developed it has the exclusive right to sell it for 20 years. Following this, other manufacturers can produce generic versions of the drug, which have the same ingredients and quality requirements as the branded product, but are usually 80% cheaper.

In recent years, several effective and widely used antiretroviral drugs have come off patent, meaning that cheaper generic versions are available.

But pharmaceutical companies often try to extend the period of time in which they have exclusive, patented products in the market. One way they do this is by developing single-tablet regimens. For example, a drug called efavirenz was first produced in the 1990s and came off patent in 2013. But efavirenz is also an ingredient in Atripla, along with two other drugs, tenofovir and emtricitabine. This single-tablet regimen first became available in 2006 and will remain under patent for several more years.

Doctors have a choice when this is the most appropriate treatment for someone living with HIV. They could prescribe the exclusive, branded version (Atripla) at a cost of several thousand pounds per patient, per year. It has the advantage that the whole treatment is one pill a day. Or they could save several hundred pounds on each patient by prescribing the same combination of drugs as two or three separate tablets, including a generic version of efavirenz. Much bigger savings could be made by making small adjustments to the drugs prescribed, using drugs of equivalent effectiveness that are available in generic versions.

But would this mean that people would have poorer results? Would more people have trouble maintaining an undetectable viral load? Would there be more cases of drug resistance?

To answer this question, researchers searched for all randomised clinical trials which compared co-formulated tablets (containing two, three or more drugs) with regimens made up of multiple tablets. They found nine studies involving a total of around 2500 people.

They found that the clinical results were as good with multiple tablets as with co-formulations. They concluded that the benefits of single-tablet regimens have not been proven, despite the large differences in costs.

You can find out more about generic medicines in NAM’s booklet ‘Taking your HIV treatment’ and in a 2012 article from ‘HIV Treatment Update’.

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Treating HIV/AIDS: growing tensions over traditional medicine, medical science. 6/3/2015

Published at 702
Written by 26 February 2015


Some South Africans are receiving incorrect guidance from families and fraudulent traditional healers, advising them to discontinue antiretroviral (ARV) therapy in favour of African traditional treatment. The concern is that traditional medicine has not been sufficiently tested using clinical trials, and the health benefits remain scientifically inconclusive. It is also reported that fake healers claim to provide cures for HIV/AIDS.

John Robbie spoke to Dr. Yogan Pillay, Deputy Director General at the Department of Health as well as practicing traditional healer and President of the South African Traditional Healers Association, Sazi Mhlongo.

Pillay encourages people to continue their ARV treatment, as HIV is a chronic disease. Mhlongo advised that traditional healers will only administer supplementary medicine to clients, but will never advise them to discontinue ARV treatment.

It is sensitive but we need to figure out how the two healing systems can work harmoniously together. Clearly we don’t want to be disrespectful of traditional healing systems, but we need to figure out how best to make them co-exist.

Dr. Yogan Pillay

Testing and research

Pillay agreed that there is need for greater testing and regulation by the Medicines Control Council. He said that modes for testing traditional medicine need to be established and that more South African research is needed on the matter. He advised that Western medicine procedures are standardized and that similar measures must be put into place to test if traditional medicines are safe and effective.

Clinical trials and collaborations

As it turns out there are tests and experiments and clinical trials underway using traditional medicine. The medical research council together with the University of the Western Cape have some trials going on. The Council for Scientific and Industrial Research has an interest in pursuing this.

Dr. Yogan Pillay

The scales of the clinical trials are not pitched at the same level as Western medicine, but there are some trials going on. According to Pillay greater effort is needed to get traditional healers to be part of the clinical trial process and to share details of the ingredients used in their medicines. However, he noted that there is often a reluctance to do this because of concerns around intellectual property.

Fraudulent healers

Mhlongo says that the problem is that there are people who claim to be traditional healers when in fact they are not. Some of these imposters suggest that they can cure HIV/AIDS and others concoct so-called ‘cures’, mixing ARV tablets with their herbs. The traditional healer said that they do not dispense traditional medicine mixed with any other drugs.

Traditional healers have been instructed not to tell people to drop ARVs. But the inauthentic healers say all sorts of things and that gives us a very bad name. There are those that are just mushrooming – charlatans.

According to Mhlongo, in Kwa-Zulu Natal, traditional healers were previously trained, examined and given practicing licenses. It has now become difficult to discern qualified healers from impostors.

He says the association has urged the government to investigate these matters and the Council of Traditional Healers will also undertake to investigate as well.

Listen to the full conversation below:

 

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Africa: A Research Agenda for HIV Survivors, 5/3/2015

Published at SAFAIDS
Written by AllAfrica
4 March 2015


EMORY, 4 March 2015 (SciDev) - Over 35 million people worldwide are living with HIV. Massive global efforts and investments to deliver combination antiretroviral therapy (ART) have transformed a fatal infectious disease into a chronic, treatable disease.

HIV-infected people who comply with ART now have near-normal lifespans - but as a result they may face the new threat of chronic noncommunicable diseases (NCDs). Stress, stigma, aging and HIV-related inflammatory changes increase the risk of some cancers as well as diabetes, heart disease, stroke, chronic kidney disease and mental health problems.

The huge gains made from implementing ART globally - 13 million people now get this treatment, nearly 90 per cent of whom live in low- and middle-income countries (LMICs) - will be lost unless the rise of NCDs in HIV survivors is addressed. High-income nations have been tackling this challenge since 1996, and it is time to do the same in LMICs too.

Uncertain risk

The problem of NCDs in HIV positive people in LMICs has been under-appreciated. This is partly due to scarce data and patchy evidence.

The extent to which HIV positive people who live in LMICs are at higher risk of NCDs than people who are HIV negative is unclear - as are the factors that might put them at higher risk. We also don't fully understand whether HIV positive people differ from the general population in the disease patterns for various NCDs, either due to HIV itself or its treatment.

For example, some studies have suggested that certain ART treatments may increase the risk of diabetes. There are also concerns about how ARTs may interact with drugs commonly used to manage NCDs. Some conditions, such as infectious myocarditis and other heart conditions associated with opportunistic infections, may be of special concern in countries where the prevalence of infectious disease, malnutrition and other poverty-related conditions is relatively high.

But a more important question is this: how must effective systems be developed to deal with NCDs among HIV survivors in regions facing severe resource constraints?

Multipronged research

Answering these pressing questions will require a multipronged research agenda.

First, it will take sound public health surveillance - data from good systematic collection systems and from studying groups over long periods - to measure the burdens of NCDs and their risk factors in HIV positive populations, and to compare them with HIV negative people.

These data will also enable estimation of the health and economic impacts of NCDs in HIV infected populations such as the cost to individuals, families and society, and the cost-effectiveness of managing disease. Such economic estimates can help with advocacy and to inform policy on where to invest scarce resources.

The second element is basic and clinical research. This is needed to investigate how inflammation, coagulation and immune mechanisms affect how NCDs develop among HIV infected people. Such research can also inform the development of diagnostics and treatments.

For resource-poor countries, it is important to have access to low-cost tools to diagnose and treat NCDs. Some tools, such as point-of-care testing and combination drug therapy, are already available; others could be developed through collaboration between academic institutions and industry.

Finally, implementing science and health systems that can deal with the rise of NCDs in HIV survivors will be crucial. This will involve generating data on the efficiency, cost-benefit ratio and feasibility of screening tests, affordable diagnostics and drug delivery tools.

It will also involve testing innovative models of integrated HIV and NCD prevention and care. Such models might include better trained health workers, and use of telemedicine and mobile phone technologies for health education, prompts to encourage treatment compliance and to connect various parts of the health system. Innovation is needed because few health delivery systems are currently integrated to allow coordinated management of NCDs and infectious diseases.

Lessons from HIV

There are lessons to be learned from the successful global fight against HIV, which was made possible through major advances in implementing treatment protocols, improving diagnostics and drug delivery, and strengthening health systems.

For example, the global health community collaborated to lower the cost of combination therapy for HIV (taking two or more drugs at a time), and to finance it in LMICs with support from organisations such as the Clinton Foundation. Collaborative work was also crucial for developing tests to identify NCD risk factors early on and low-cost combination therapy for NCDs using generic drugs, such as statins or anti-hypertensive drugs. The development and marketing of such polypills (drugs combined in a single formulation) requires firms that are interested in collaborating with academic institutions to deliver low-cost treatments.

The battle against HIV has also taught us that pharmacological approaches need to be combined with behavioural interventions, for example through promoting condom use. The same principle can be applied to NCDs.

In an era of finite res

Sources, leveraging the global HIV infrastructure to tackle the rising NCD burdens in HIV survivors is the obvious way forward. This will require active interdisciplinary collaboration.

There is some low-hanging fruit. Establishing studies to compare the incidence of NCDs between HIV positive and negative people, for example, can leverage existing surveillance or clinical trials data on groups of HIV positive people. Other immediate steps forward could be to evaluate integrated delivery interventions for combined HIV and NCDs, and to test how mobile technologies can help enhance compliance with treatment and train healthcare staff.

Building on HIV control platforms developed from internationally funded initiatives such as PEPFAR (US President's Emergency Plan for AIDS Relief) and the Global Fund to Fight AIDS, Tuberculosis and Malaria would serve as a good start.

K. M. Venkat Narayan is the Ruth and O. C. Hubert Chair of Global Health, professor of epidemiology and medicine, and director of the Emory Global Diabetes Research Center at Emory University, United States. Sten Vermund is director of the Institute for Global Health and professor of paediatrics, medicine and health policy at Vanderbilt University School of Medicine, United States. Narayan can be contacted at knaraya@emory.edu and Vermund at sten.vermund@vanderbilt.edu

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Demedicalizing AIDS Prevention and Treatment in Africa. 4/2/2015

Published at The New England Journal of Medicine
Written by Tom Ellman
22 January 2015


Audio Interview with Lynne Wilkinson on a community-based strategy to promote HIV treatment adherence in South Africa. (07:24)

At the recent World AIDS Day celebrations, national and organizational commitments to support affected communities, meet treatment and prevention targets, and expand access to antiretroviral therapy (ART) were asserted once again. Yet the reality in much of Africa suggests that AIDS is far from over.

Since 2002, ART programs have been slowly rolled out in Africa. Initially, HIV-infected people had to wait until they were seriously immunocompromised, with a CD4 T-cell count below 200 per cubic millimeter, to begin ART. The threshold was raised to 350 and then 500, as the importance of earlier initiation of treatment was recognized. Improved tools and strategies followed, as did consensus on treatment guidelines and international funding. The trajectory toward ending AIDS seemed assured, and international goals grew from “3 by 5” (treating 3 million people by 2005), to “15 by 15,” to a call from the Joint United Nations Program on HIV/AIDS for “90-90-90” by 2020: 90% of people living with HIV tested, 90% receiving treatment, and 90% with an undetectable viral load.

Close examination of the HIV epidemic, however, reveals that all is not well. In South Africa, home to the world's largest ART program, for instance, 25% of patients who begin ART are lost to follow-up by a year later, and in 25% of treated patients, viral suppression is not achieved.1 In many countries, rates of retention in treatment are worsening, the incidence of HIV infection among young women remains shockingly high,2 men are tested and initiate treatment late in the course of infection and often not until they have advanced disease, public-sector facilities are overloaded with patients and plagued by medication stock-outs, and donor funding has flatlined for the past 6 years.3 Perhaps most important, the activist groups that have held governments, health systems, and the international community accountable are at best underfunded and at worst sidelined, jaded, and mute. South Africa's Treatment Action Campaign, which played a major role in ending denialism and starting the ART rollout in the country with the largest HIV-positive cohort, faces a major funding shortfall.4 As one panelist remarked at a conference of the Southern African HIV Clinicians Society last September, “The honeymoon is over.”

A major contributor to these problems is the burden placed on patients and health care facilities by the failure to simplify treatment for healthy HIV-positive people. Clinics overloaded with the healthy are unable to focus high-quality care on patients with the greatest need.

As guidelines edge closer to universal treatment for HIV-infected people regardless of CD4 count, more people can choose to receive ART before they develop symptoms. Earlier treatment represents an opportunity not only to prevent illness and transmission but also to inform and empower people living with HIV–AIDS while reducing the burden on health care systems. Rather than seizing this opportunity by demedicalizing the provision of ART, however, programs are medicalizing HIV infection in the healthy.

In most of Africa, despite shortages of health workers, initiating ART in a healthy HIV-positive adult means the start of monthly queues at clinics and pharmacies to see overburdened medical staff. To obtain treatment, such patients face long walks to health centers or high transportation costs, hours of queuing, and poor, sometimes stigmatizing, consultation. Unlike symptomatic patients, these patients see no short-term benefit from treatment. Unsurprisingly, they often adhere poorly to ART regimens or rapidly stop them altogether. Many health care workers believe such patients should not be offered treatment, so that clinic staff can concentrate on sick patients.

The experience of Médecins sans Frontières and others suggests that the solution is not to deny people earlier treatment but rather to implement policies and strategies that reduce the burden associated with their care. Such policies and community-based models of care are already well described,5 endorsed by the World Health Organization, and included in national guidelines, but theoretical commitment to them is not matched by funding.

Like other chronic disease treatments, ART is best taken at home, with pills available through repeat prescription at local pharmacies or even by mail. A viral-load test performed every 6 or 12 months can inform HIV-infected people if they're doing well and need no medical care, just as glycated hemoglobin tests inform diabetic patients.

Healthy patients require community-based adherence support backed up by robust systems for monitoring and evaluation, drug delivery, and laboratory testing. Those in need of medical care — for initiation of ART, when sick or suffering from medication side effects, or because of high viral load or low CD4 count — must be distinguished from those who are not.

Five elements of this approach are worth highlighting. First, drug delivery should be patient-centered: it should fit into patients' lives, requiring minimal time and being delinked from clinical consultation. Stable, healthy, HIV-infected people taking once-daily, low-toxicity regimens could receive refills lasting at least 3 months from a facility close to their home, with little or no queuing. Ideally, various fast-track options, including community pharmacies, would be available. Community ART groups and adherence clubs (see the Perspective article by Campion, pages 301–303) can further minimize the burden, with one person picking up drugs for several others. Such approaches save costs and enhance retention and should become the norm rather than the exception.

Second, annual viral-load measurement should replace routine CD4 testing for stable, healthy ART recipients. Such assessment provides an objective measure of treatment effectiveness and can assuage clinicians' doubts regarding adherence. If a test on dried blood spots (with results delivered directly to patients and clinicians, by text message where possible) revealed an undetectable viral load, the patient could continue receiving “minimal-burden care,” with an annual clinic visit. A high viral load should trigger a counseling intervention to address adherence, ideally at the community level, backed up by clinical screening and regimen changes as necessary, until the virus is suppressed. It would not necessarily mean shifting the patient from low-burden care, which could further worsen adherence.

Third, monitoring and evaluation are essential for informing patients, providers, and the health system but have not been adapted to systems operating outside facility-based clinical care. The lack of a functional monitoring system leads to government and donor mistrust of community-based support and drug-delivery strategies, and investment is needed to develop integrated systems. Such systems should also support HIV-positive communities to monitor the quality of their care and hold the government accountable for drug stock-outs or other deficiencies.

Fourth, all these activities depend on trained individuals and funded, coordinated structures operating at the community level, near where HIV-infected people live. Currently, most interventions depend on volunteers, nongovernmental organizations, or scarce and underfunded health-center outreach and community health workers. Capacity for managing support groups, promoting HIV testing and linkage to care, identifying at-risk patients, monitoring effectiveness, and supporting adherence can be established at the community level, but not without support and funding. Such services pose no threat to the health sector; rather, greater investment in community capacity should be seen as essential to population health.

Finally, independent civil-society activism, rooted in affected communities, remains critical to sustaining an effective, accountable response to HIV and health care in general. Paradoxically, with successful ART rollout has come a decline in community activism. Engagement with the strategies described here can contribute to stronger community structures, but increased funding is essential to ensure that HIV activists' voices are heard.

This approach is not a panacea. For many communities, treatment coverage remains unacceptably low. The very concept of “community” varies with the context, and community engagement does not reduce government's responsibility to provide high-quality clinical care. Efforts to strengthen health system capacity and end the crisis in human resources for health must not be compromised. Nonetheless, a shift from facility-based medical care to shared responsibility with community-based “wellness” support could transform not just the HIV landscape but care for noncommunicable diseases and health in general.

Perhaps the threat of vast increases in the number of healthy people on ART is the impetus the health system, policymakers, and donors require to match their rhetoric with investment. Until they do, the 90-90-90 target, let alone the end of AIDS, will remain a pipe dream.

 

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Treatment News 2014

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START Study Could Change How We Look at HIV Treatment, and HIV Itself. 21/11/2014

Published at The Body
Written by Simon Collins
21 November 2014


Have you heard of the START (Strategic Timing of Antiretroviral Treatment) study? In my opinion, it is probably the most important study currently running. It generates strong views, both for and against initiating antiretroviral therapy early, but the results are likely to be surprising.

Let's look at what START will and won't tell us about "when to start" treatment.

As an activist living with HIV, I want decisions about my care to be supported by evidence. Jumping ahead of the data -- even with the best intentions -- has led to treatment guidelines in the past getting it wrong. So, over the last five years, I have been surprised at how passionately some people object to START, already claiming to know the answers.

The big question from START is whether there are better health outcomes from starting antiretroviral therapy with a CD4 count above 500. This is compared to waiting until 350 -- a level at which we already know it is good to start.

No other randomized study had answered this.

And the answer to this question is not obvious. Here's why:

Even though many people already start treatment early and do well, people can reach "normal" life expectancy by just starting above 350. On the other hand, many people start far too late -- and if START shows benefits at very high CD4 counts, this could change guidelines globally.

Some questions in START are about fine tuning: Everyone in the study is lucky enough to have been diagnosed early and has access to antiretroviral therapy.

But START will also define the risks from earlier treatment. This includes direct risks such as side effects, which we expect to be low. It also includes long-term risks such as drug resistance. If earlier treatment has lower adherence rates, this might mean some people lose treatment options without any medical benefit.

The Power of a Large, Randomized Study, and Its Sub-Studies

START is important because it is a very large, randomized study. Between December 2009 and January 2014, more than 4,600 people were enrolled from 36 countries. By not letting people chose whether they start early or late, other factors that affect the results are also likely to be balanced in each group. This includes education, income, motivation, recreational drug use, smoking, country, coinfection and even genetics. The size of the study means that it is large enough for the outcomes to be real rather than by chance.

Just as crucially, the sub-studies in START look at major scientific issues about HIV itself. These may prove even more important than the main question of when to start. Everyone entering the study has a "normal" CD4 count when they join. This means the results will compare the effect of HIV on the brain, on bone health and on lung health to the effect of HIV treatment.

For example, we already know that antiretrovirals reduce bone density by a small amount (in addition to the reduction in density caused by HIV and any reduction caused by aging). If there is a similar negative impact of antiretrovirals in the brain, we need to know this. Currently, it is considered more important to control HIV, but we need data if early treatment is going to be widely recommended. Also, the lung disease called COPD -- principally linked to smoking -- is the third leading cause of death globally. While many doctors hope that early antiretroviral therapy might help, we need to know whether this is true.

All these examples overlap with issues of aging and with mental health, both of which have a complex relationship to HIV. By studying a few thousand people in early infection, START will provide data that could affect millions of people.

Quantifying Individual Health Benefits Versus Public Benefits

It is important that START will quantify individual health benefits compared to risks because many countries, including the U.S., already merge the personal and public benefits of earlier antiretroviral therapy in policies aimed at reducing new infections.

But many of us never risk passing HIV to anyone else. For example, we might not be sexually active, our partner(s) may also be HIV positive or we might always use condoms. These are just three situations that show why the decision to start treatment may often be purely focused on clinical benefits versus risk for the individual. To inform this decision, we need data, not guesswork.

There are lots of theories about why reducing viral load earlier in infection might be good. But, it might not be. Or it might not make much difference, so long as when you do start treatment you take it in the right way. This would be another significant finding. Sometimes people need -- or want -- time before deciding to start.

Prepare to Be Surprised

START will not show the best CD4 count for starting treatment. But, it will quantify how safe and effective earlier treatment can be. It will not show drug safety for antiretrovirals that were not yet approved. But this is true of every study. The big picture for START is to define the risks from uncontrolled HIV when the immune system is still strong. This is not primarily about individual drugs.

The SMART researchers ran another large, randomized study about 10 years ago. Many people then were convinced that taking a treatment break would be safe. This included leading doctors, researchers and activists -- and a large percentage of HIV-positive people.

It was only with a large, randomized study that this belief was overturned. The results from that study -- so strong that they were determined to be conclusive years earlier than anticipated -- surprised nearly everyone. That study was called SMART, and it radically changed the direction of HIV research.

So, no one is helped by second-guessing the results from START. For example, some benefits might have to be offset against some downsides. Or the risk versus benefit balance might be stronger for some people to start earlier and for other people to wait. Although guidelines always try to simplify recommendations, they also emphasize that antiretroviral therapy should be individualized.

Whatever the actual results, the value of START includes the quality of the evidence. It will include a large sample and data set that will help answer many other questions.

Results are expected by early 2017. Until then, people have to use their judgment and preferences when choosing when to start. Current guidelines emphasize the advantages and disadvantages of the various options.

But by World AIDS Day 2016, the study will wrap up the collection of a tremendous amount of data that can go on to inform both individual decisions and public policy. The results from START -- and similar "when to start" studies -- will be a significant achievement that will inform guidelines and care globally. The most useful prediction is to be prepared to be surprised.

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AIDS 2014: New drug license step forward in meeting HIV treatment needs.

Published by EAA

The Ecumenical Advocacy Alliance (EAA) welcomes the agreement announced today at the 20th International AIDS Conference in Melbourne between Gilead Sciences and the Medicines Patent Pool (MPP) that extends their current license to include tenofovir alafenamide (TAF). The agreement will allow access to generic formulations of TAF in countries accounting for 92.2% of people living with HIV.

TAF, along with new medicines such as dolutegravir, are important drugs for future HIV treatment that will likely mean safer, effective, and more affordable antiretroviral therapy, improving care for people living with HIV. TAF is currently in Phase III clinical trials and could be approved by the United States’ Food and Drug Administration in 2015. Dolutegravir is already available for generic manufacture via the license agreement between MPP and ViiV Healthcare on 1 April 2014.

“We applaud Gilead Sciences for extending their license with MPP to include new drugs that can significantly expand options for first-line treatment for many people living with HIV,” said Astrid Berner-Rodoreda member of EAA’s Access to Treatment Working Group and HIV advisor for Brot für die Welt. “The inclusion of China as a manufacturing country in addition to India is also a step forward in expanding opportunities for generic production and competition which should bring prices down.”

She is concerned, however, that the 5% royalty fee requested is too high, and that the license is not as broad as that for dolutegravir, which included the public sector of some middle-income countries in an innovative pricing scheme. “The ability for people living with HIV in middle-income countries to access affordable HIV medicines is still essential,” she stated.

The MPP negotiates with pharmaceutical companies to share their HIV medicine patents with the Pool, and then licenses generic manufacturers to facilitate the production of affordable medicines well-adapted for use in resource-poor settings. Since the MPP Foundation was formally established in 2010, it has concluded agreements with four pharma companies: Gilead, ViiV Healthcare, Roche, and BMS.

Members of the Access to Treatment working group hope other pharmaceutical companies will follow Gilead’s lead in negotiating and reaching agreements with MPP.

“We urge other companies to follow the example that ViiV, Gilead Science and BMS have set to enter negotiations with the Pool and reach agreements that can bring life-saving medications within reach for millions,” concluded Berner-Rodoreda.

“The EAA has been involved in advocating with pharma companies to place their patents into the pool since the inception of the MPP,” states Pat Zerega, corporate responsibility consultant to the Evangelical Lutheran Church in America and member of EAA’s working group. “The faith community through our work in many countries, especially those with few resources, is very aware of the increasing need for access to HIV drugs.”

For more information contact: Sara Speicher, sspeicher@e-alliance.ch,
+44 7821 860 723.

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Activists call for “Undetectable” viral load for all by 2020! 21/7/2014

Published by TAC in E-Newsletter.

Treatment Action Campaign • Treatment Action Group • HIV iBase • International Treatment Preparedness Coalition (ITPC) • Health GAP • AIDS and Rights Alliance of Southern Africa (ARASA) • Asian Network of People Living with HIV/AIDS (ANP+) • MSF Access Campaign • AfroCAB • International Community of Women Living with HIV/AIDS East Africa (ICW EA) • AIDS Law Project, Kenya • Housing Works • TASO Uganda • Zimbabwe Network of People Living with HIV/AIDS (ZNNP+) • Positive Generation Cameroon • International Civil Society Support • Thai AIDS Treatment Action Group (TTAG) • Thai Network of People Living with HIV (TNP+) • ACCESS Foundation Thailand • Delhi Network of People Living with HIV (DNP+) • National Network of Tanzanian Women with HIV/AIDS • Africa Young Positives (AY+) • Africa Japan Forum • Japan AIDS and Society Association (JASA) • Gays and Lesbians of Zimbabwe • Treatment Advocacy and Literacy Campaign (TALC), Zambia • Coalition for Health Promotion and Social Development (HEPS) Uganda • DRC National Grassroots Association of People Living with HIV • Zimbabwe HIV/AIDS Activist Union Community Trust (ZHAAUCT) • Ngibalulekile • Services for Health in Asian and African Regions (SHARE) • Rede Nacional de Asoociaçiões de Pessaoas Vivendo Com HIV/SIDA • National Association of People Living with HIV, Mozambique (ENSIDA) • Movement for Access to Treatment In Mozambique (MATRAM) • Mozambique Association of AIDS Service Organizations (MONASO) • Mozambique Network of NGOs working In Health and HIV/AIDS (NAIMA+)

“Undetectable” viral load—opportunity for all by 2020!

We call for an ambitious target of undetectable viral load to form the core of new global goals being debated by United Nations institutions and national governments and demand not just the promises but the funding, treatment options, laws and policies needed to meet those targets.

To achieve success in the fight against the HIV epidemic, reporting and tracking HIV testing and treatment as success indicators are simply not good enough.  We need to know how well HIV-positive people are actually doing. Currently, reaching and maintaining an “undetectable viral load” is the closest thing we have to a cure for HIV. The best measure of whether HIV is being suppressed in an HIV-positive person’s body is a viral load test. Durable suppression of HIV helps HIV positive people stay alive and healthy while also helping prevent HIV transmission through sex, injecting drug use, and during pregnancy, labour and breastfeeding.

Yet today most people living with HIV outside wealthy countries don’t know their viral load and too many do not have the treatment they need to control the virus—often because they do not even have access to testing. This is a violation of basic human rights—all people deserve the information, medicine, and support needed to control and suppress the virus.

We must therefore be monitoring viral load suppression rates to ensure HIV treatment programmes are delivering maximum impact for HIV positive people. Viral load tests are also recommended for the optimal management of people receiving antiretroviral treatment. The World Health Organization recommends routine viral load monitoring to ensure antiretroviral treatment is working and to ensure timely and accurate detection of treatment failure.  

In addition, the cost-effectiveness of viral load testing is improving and new technologies promise further price reductions, along with expanding economies of scale. We do not consider cost to be a sufficient excuse for failing to offer every person on antiretroviral treatment on the planet an annual viral load test by 2020. We also do not consider a lack of current testing capacity in some developing countries to be either an insurmountable obstacle or an acceptable excuse. When ARV treatment was introduced in the early 2000s, sceptics argued that providing treatment in resource-limited settings would be impossible due to cost, complexity and lack of technical capacity.The same arguments are being used today regarding viral load monitoring, even though the benefits of the technology are indisputable.

We know, too, that viral load monitoring is just one piece of the puzzle. To achieve undetectable targets leaders must commit to:

  • Using every tool available to eliminate patent barriers that make ARVs and other drugs unaffordable in many countries.
  • No single viral load test anywhere in the world should cost more than 10 USD and further price reductions should be possible.
  • Fully funding the HIV treatment response including fully funding national programs, the Global Fund, PEPFAR, and other initiatives.
  • Fully funding strong, accountable, community-based treatment literacy and adherence support along with strong social protection programs. 
  • Committing to a human rights based HIV response by combating criminalization, discrimination, and stigma and averting coercive practices by putting in place a strong community led rights infrastructure.

If United Nations agencies and national governments are serious about truly turning the tide against the HIV epidemic, they will set ambitious viral load suppression targets and ensure that everyone has the opportunity to have an ‘undetectable’ viral load. The target we want is as follows: “At least 80% of all treatment eligible HIV-positive persons must have undetectable viral loads by 2020 (persons who did not have viral load tests in the preceding 12 months must be considered not to be virally suppressed).”[1]

For more information contact:

Marcus Low: 082 962 8309 / marcus.low@tac.org.za



[1] At least 80% of ALL treatment eligible people must have undetectable viral loads by 2020, which means a significant increase in voluntary HIV testing and enrollment on treatment and care programs, reflecting that 90% of people eligible for ART have access, and 90% of people on ART reach and maintain an undetectable viral load.

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No reason to skip a dose. 22/10/2014

Published by By on Health-e News.

HIV and tuberculosis remain leading causes of death in South Africa. Now, Anova Health Institute’s Dr Khanyi Tshabalala responds to the top five reasons tuberculosis (TB) and HIV patients give for skipping their daily doses.

 

Taking treatment for multidrug-resistant TB can involve handfuls of pills for two years but Dr Khanyi Tshabalala urges patients to try and see treatment through.

Taking treatment for extensively drug-resistant TB can involve handfuls of pills for two years but Dr Khanyi Tshabalala urges patients to try and see treatment through.

In March, Statistics South Africa released its latest data on what is killing South Africans. TB remains the leading cause of natural death in the country. Although HIV-attributable deaths continue to decrease slowly, HIV also remains among the top ten causes of death in the country.

According to the latest statistics in Parliament, about six percent of TB patients default on their daily treatment. Meanwhile, about 40 percent of South African antiretroviral (ARVs) patients cannot be traced three years after starting treatment, according to a recent joint review of the country’s HIV and TB programmes.

Community health workers from Douglas, Northern Cape about 100 km outside of Kimberley recently gave OurHealth the top reasons their patients cited for skipping daily doses of HIV and TB treatment.

OurHealth asked Dr Khanyi Tshabalala from the Johannesburg-based Anova Health Institute, which specialises in HIV and TB, to respond and set the record straight.

Reason: The Department of Health does not know my immune system, how can they tell me what treatment to take?

Dr Tshabalala says: “Nurses and doctors working at the clinic will do blood tests on all HIV-positive patients. They test for what we call “CD4 cells,” which are the body’s immune cells. These cells are like soldiers who fight infections. These soldiers, or immune cells, are reduced in HIV and that tells us that the immune system is weak.

“HIV and TB treatment has been scientifically proven to work. This means that the drugs you have been prescribed have been tested in thousands of volunteers over many years as part of randomised controlled clinical trials. After they pass these tests, these medicines must also meet government standards. In South Africa, the drug regulator the Medicines Control Council has approved all the drugs you have been prescribed for use in the country.

“Currently, antiretrovirals (ARVs) are the only treatment known to be effective in controlling HIV. If used properly, ARVs can dramatically increase your lifespan. Meanwhile, taking TB treatment daily can not only cure you and protect others from contracting it from you but it can also make sure you don’t develop worse forms of TB.”

Reason: I feel nurses deliberately treat me poorly because of my disease. I’d rather stop going to the clinic than continue to suffer abuse I can do nothing about.

Dr Tshabalala says: “No patient should be treated badly by any staff working at the clinic. Every patient has the right to dignity and respect, and that right is a priority to the Department of Health. Every patient has the right to complain or report any abuse by staff to the clinic manager or local authority of their community to ensure that it does not occur.”

Reason: I don’t feel sick and don’t see why should I keep taking treatment?

Dr Tshabalala says: “Even when HIV patients do not feel sick, it is important for them to continue their treatment to prevent them from being sick. The treatment is taken in order to control the virus and protect the immune system so that patients can feel well. Treatment should be taken for life and never stopped. If HIV treatment is stopped, the virus will increase again and the immune system will suffer, which will lead to illnesses such as TB.

“TB patients are likely to feel better before they are fully cured. TB patients should continue to take their treatment until their nurse or doctor tells them to stop to prevent infecting others or developing worse forms of the disease.”

Reason: The pills for HIV and TB treatment are too big and bitter to swallow.

Dr Tshabalala says: “Over the years, there has been an effort to make treatment options easier for patients. Most HIV patients are now on one pill, which is a combination of three ARVs in one. This one pill is taken once a day at night only. This makes it easier for patients to stay on their treatment. There is a lot of work to make sure that even if patients do not qualify for the one pill, they are put onto a choice of drugs that need to be taken once daily.

“With regards to TB treatment, it is a course of six months only. Unlike HIV, TB can be cured if the course of treatment is completed as prescribed. Treatment for drug-resistant forms of TB can take much longer and have very difficult side effects but it’s important to always finish your course.”

Reason: If I am taking TB treatment, why do I have to stop using drugs, smoking or drinking?

Dr Tshabalala says: “TB treatment should not be taken with alcohol or other drugs as the combination can be damaging for the liver. We encourage our patients to maintain a healthy diet and lifestyle in order to help with speedy recovery, and maintain a healthy body and mind.” – Health-e News Service.

 

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African Studies Identify Strategies for Improving Treatment Adherence, Retention in Care - 29 Jan 2014

Getting people tested for HIV is one thing; getting them onto antiretrovirals (ARVs) another; and retaining them in care for a long period something else entirely writes Mara Kardas-Nelson via AIDSmap.

A session at the 17th International Conference on AIDS and STIs in Africa (ICASA) in Cape Town, South Africa, last month, considered which patients are least likely to be retained in care, and innovative strategies to keep patients in care in the long run, using limited resources.

By retrospectively analysing data from patient files between February 2002 and May 2013 at a clinic in Masaka, Uganda, Juan Gozalez-Perez of the AIDS Healthcare Foundation presented findings showing that patients were more likely to die and least likely to be retained in care in their first year after diagnosis; and that men, adolescents aged 15-29, and those with a CD4 under 100 were least likely to be retained.

The study considered 12,475 patients, with 'lost to follow-up' defined as a patient not presenting for care 90 days after the last missed appointment. In the cohort, 2216 patients were lost to follow-up, 971 died, and 1734 were transferred out. Of these, 61.1% were female with a median age of 32.2 years and a median CD4 baseline of 162. Of those lost to follow-up, one-third of patients could not be reached, 11% had died, 24% were transferred out or not documented, 19% were alive and not taking their ARVs, 6% self-referred out, and 4% had their files lost.

The greatest loss to follow-up occurred in the first year of treatment. After one year, retention rates were 82.4%. Thereafter the rate of attrition was relatively consistent, and 63% of patients treated for ten years remained in care. Female patients were more likely to be retained, with 83% of women, versus 81% of men, being retained in their first year, and 63% of women, versus 58% of men, retained at 10 years. People aged 15-19 fared worse, with retention rates of only 43% at five years, compared with 70% in the overall cohort.

While their study did not consider rates of retention of people not yet on ART, Gonzelez-Perez noted that patients in pre-ART care, such as those taking cotrimoxazole, are even harder to retain. "We need to work more on this, it's a completely different situation."

A retrospective analysis of routine patient data in Shiselweni district, Swaziland, presented by Kiran Jobanptura of Médecins Sans Frontières (MSF) Swaziland and Switzerland, found that children and adolescents were less likely to re-suppress when considering viral load for patients in the Shiselweni district of the country, indicating that this group of patients may need tailored adherence and genotyping support.

By considering records of patients who had a first detectable viral load attending Ministry of Health facilities in Shiselweni between May 2012 and July 2013, MSF also found that those with a viral load under 1000 copies/ml, with a CD4 under 350, and who did not receive counselling were more likely to re-suppress viral load after an adherence intervention. In total, 54% of patients observed achieved re-suppression. Surprised by results that counselling did not lead to re-suppression, Jobanptura notes that treatment literacy may offer an explanation. "Just receiving detectable results, without counselling, may enable patients to re-suppress," he said, also noting, "we cannot say that we're doing the counselling in the optimal way." Currently the project is using lay counsellors who receive limited training for counseling, as nurses are in short supply.

Stategies for retention in care

Two South African interventions are looking at how to retain long-term ART patients in care in a way that reduces the time they need to go to and wait at clinic – freeing up their own time, the time of healthcare workers, and decongesting overcrowded clinics.

Anna Grimsrud, a doctoral student at the University of Cape Town, presented data on ART adherence clubs in Gugulethu and Khayelitsha, townships just outside of Cape Town, South Africa. In clinics here, MSF South Africa and the Desmond Tutu HIV Foundation support clubs which allow long-term, stable patients – defined as those in regular clinic care on ART for two years, with a suppressed viral load and without another chronic condition, to meet outside of a clinic setting every two months to collect their medication. They are supported by a community healthcare worker who leads group counselling sessions and takes basic clinical measurements such as weight. Participants only have one clinic visit each year unless health issues arise.

The clubs have been going for several years now, and last year patients were given four-months ART supply over the Christmas holidays, with the intention of limiting patient interruptions. Grimsrud notes that many patients travel from Cape Town to homes in the Eastern Cape and other provinces throughout the holidays, and therefore miss their adherence club appointments.

Grimsrud notes that there was no difference in the percentage of patients falling out of care when given two-month versus four-month supply. Because of the positive results, this year all adherence club patients are receiving a four-month supply over the holidays. "We had to start to trust our patients and believe that a 4-month supply was best for them, and that they would return to us after," she said, further noting, "these findings have led us to ask: what is the optimal visit frequency for stable patients?... The adherence club model is just one model of care. We understand that there's a whole complex package of what can be done for patients. We need more operational research and data."

An in-clinic model has been used at the Ithembalabantu People's Hope Clinic in Durban, South Africa. Here, stable, long-term patients are only seen by a clinician every six months, and pick up their ART every two months in a "fast track wing" at the clinic. Staffed by two healthcare workers who check the patients’ vital signs and hand out drugs, the wing is able to support 1200 patients a month.

Terisha Maharaj of the AIDS Healthcare Foundation, which owns the clinic, says the intervention has significantly reduced waiting times. In quarter one of 2013, before the intervention was fully at scale, 33% of people in the clinic waited less than 1-2 hours, with 61% spending 4 hours waiting. In the third quarter of 2013, more than 51% of patients were in and out of the clinic within 1-2 hours, with 47% waiting 2-4 hours. From February 2013, when the intervention was implemented, until May 2013, daily client visits increased from 967 to 1736. Over time, patients in the fast-track wing are picking up their drugs more regularly: in February 2013, just after the intervention was implemented, 13% didn't pick up their drugs, but in November 2013, only 2.2% failed to pick up their drugs.

Maharaj says the intervention is better for all patients – those in the fast-track wing, and in the regular clinic, and healthcare workers. "If you have a large, congested clinic you weigh down your human resources. This is a form of task-shifting, and also helps us to see more critical clients." Maharaj also said that reducing waiting times affords patients more opportunities to pursue work and family life. "We want them to be gainfully employed so that they don't have to rely on aid. When people are working, you achieve the economic benefits of ART. You have an economically productive and sustained population."

References

Gonzelez-Perez J et al. Rural Uganda: above 50% retention after 10 years on ART. 17th International Conference on AIDS and STIs in Africa, Cape Town, 2013, abstract ADS056. 

Jobanputra K et al. Predictors of virological resuppression following enhanced adherence counselling by lay counsellors in Swaziland. 17th International Conference on AIDS and STIs in Africa, Cape Town, 2013, abstract ADS059.

Grimsrud A et al. The impact of circular migration support utilising 4-month versus 2-month ARV refills on ART adherence clubs outcomes. 17th International Conference on AIDS and STIs in Africa, Cape Town, 2013, abstract ADS057.

Maharaj T et al. Strategies to address clinic waiting time and retention in care; lessons from a large ART center in South Africa. 17th International Conference on AIDS and STIs in Africa, Cape Town, 2013, abstract ADS058.

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Computerised Counselling for Patients Taking HIV Therapy can Reduce Viral Load, Improve Treatment Adherence and Reduce Rates of Risky Sex - 21 Jan 2014

Computerised counselling can achieve reductions in viral load and HIV transmission risk behaviour, investigators from the United States report in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The counselling programme was associated with significant reductions in viral load, improvements in adherence to HIV therapy and reductions in risky sexual behaviour.

“The adherence effect was most pronounced among those whose plasma HIV-1 load was not suppressed at baseline,” comment the investigators. “This reduced viral load and fewer sexual transmission risk behaviors seen among those undergoing the intervention both may contribute to decreasing HIV transmission to sexual partners.”

Thanks to antiretroviral therapy, many people with HIV now have a normal life expectancy. The best outcomes are seen in individuals who adhere to their treatment. Good adherence also has a secondary benefit, as suppression of viral load is associated with a reduced risk of HIV transmission to sexual partners.

Writes Michael Carter.

However, some people living with HIV have difficulty achieving and sustaining the levels of adherence associated with the best treatment outcomes, and a significant proportion of patients with HIV have sexual behaviour that involves a risk of HIV transmission.

Investigators in Seattle wanted to see if a computer-delivered intervention called Computer Assessment and Rx Education for HIV-positive people (CARE+) improved treatment adherence and reduced transmission risk behaviours.

They therefore designed a nine-month randomised-controlled trial involving 240 adult patients taking antiretroviral therapy.

The study had two arms.

Participants in the intervention arm had access to a computerised programme that provided counselling about treatment adherence, HIV disclosure, safer sex, condom use, substance abuse and the impact of adherence on viral load. Individuals in the control arm completed computerised questionnaires, answering questions about their treatment adherence, substance use and sexual risk behaviour.

The primary outcomes were changes from baseline in viral load, 30-day adherence to HIV therapy and the likelihood of reporting unprotected anal/vaginal sex or problems with condom use.

The participants had an average age of 45 years and approximately 90% were male. Participants reported taking a median of 76% of their treatment doses at baseline. Sex without condoms or condom problems were reported by approximately 30% of people on entry to the study, and viral load was detectable in a similar proportion of individuals.

The study was completed by 87% of the participants.

There were marginally significant differences in viral load changes from baseline to the end of the study between the study arms (p = 0.053). People in the intervention arm had an average decrease in viral load of 0.17 log10 copies/ml, compared to an average increase of 0.13 log10 copies/ml among people in the control arm. Compared to baseline, the chances of having an undetectable viral load at the end of the study increased significantly for people in the CARE+ arm (p = 0.037) but fell non-significantly for people in the assessment-only arm.

Among the study participants who had a detectable viral load at baseline, the people receiving computerised counselling had an average decrease in viral load of 0.60 log10 copies/ml (p = 0.004), while the control group participants had an average non-significant increase in viral load of 0.15 log10 copies/ml. At the end of the study, viral load was a significant 0.73 log10 copies/ml lower among people in the intervention arm (p = 0.041).

The intervention also had a significant impact on adherence. This increased by approximately 5% (p = 0.014) among people receiving computerised counselling, but fell by a non-significant 1.4% among people in the control arm.

Focusing on participants with a detectable baseline viral load showed CARE+ intervention participants had an average increase in adherence of 8% (p = 0.04), whereas the control patients had a non-significant decrease of approximately 1.5%. At the end of the study, adherence was a significant 13% higher (p = 0.038) in people in the intervention arm compared to people in the control arm.

CARE+ was associated with changes in HIV transmission risk behaviour. The odds of behaviour involving a risk of transmission were reduced by 55% among people in the intervention arm (p = 0.02), but increased modestly for individuals in the control arm. At the end of follow-up, CARE+ intervention participants had reduced odds of transmission risks compared with the controls (OR = 0.46; 95% CI, 0.25-0.84, p = 0.12).

The intervention was highly acceptable, with 97% of participants reporting it was easy to use, and 93% felt CARE+ sessions helped them as much, if not more, than face-to-face counselling sessions.

“As far as we know this is the first ART adherence and secondary transmission risk intervention to find biological effect (viral load) and behavioral impact among persons living with HIV,” conclude the authors. “The computer format was highly acceptable and facilitated delivery in busy settings. Such an approach warrants further evaluation to determine utility in improving HIV treatment outcomes and reducing secondary HIV transmission among persons living with HIV.”

Reference

Kurth AE et al. Computerized counseling reduces HIV-1 viral load and sexual transmission risk: findings from a randomized controlled trial. J Acquir Immune Defic Syndr, online edition. DOI: 10.1097/QAI.0000000000000100, 2013.

This news report is also available in Russian.

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Treatment News 2013

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New Drug License to Help Meet Growing HIV Treatment Needs. 16/12/2013

The Ecumenical Advocacy Alliance (EAA) today welcomes the agreement announced on 12 December between Bristol-Myers Squibb and the Medicines Patent Pool (MPP) that will extend generic manufacture and distribution of atazanavir (ATV), a preferred second-line treatment for adults living with HIV and also used for children over the age of six.

“This new agreement between the MPP and BMS on ATV is a breakthrough. It will enable generic competition for atazanavir, effectively increasing its availability and affordability for the growing number of people who need second-line treatment,” said David Deakin, Chair of the EAA’s working group on access to treatment and Head of HIV at Tearfund, UK. 

Anti-retroviral medicines (ARVs) are essential in managing HIV infection, and many of the first ARVs developed over 20 years ago can now be manufactured generically at a lower cost. However, individuals on treatment develop resistance to the drugs over time, meaning they need to move to more recent second-, and even third-line medications that remain prohibitively expensive in resource-poor settings. This makes it all the more important for pharmaceutical companies to place essential drugs in the MPP.

“By making it possible for ATV to now be sold at lower cost in at least 110 low- and middle-income countries that are home to almost 90% of all people living with HIV, this license is a crucial next step in our combined global efforts to make second line ARV treatment available at cheaper prices,” states Astrid Berner-Rodoreda, advisor on HIV and AIDS for Brot für die Welt and member of the EAA working group. “However we remain concerned that people living with HIV in the middle-income countries– such as Argentina, Malaysia, Philippines, Thailand and Ukraine – are not covered by this new agreement and thus are in danger of falling between the gaps, and call upon all stakeholders to take urgent action to address this issue.”

Building on the precedence of previous MPP license agreements, this new license meets many of the ‘model’ criteria called for by access to treatment advocates. “We applaud the flexibility that this license gives the Pool for manufacturing and sub-licensing as well as the transparency of this agreement,” notes Msgr. Robert Vitillo, special advisor on HIV and AIDS, Caritas Internationalis, and member of the EAA’s working group.

Since the MPP Foundation was formally established in 2010, it has concluded agreements with five companies, notably Gilead, ViiV Healthcare, Roche, and now BMS.

“Members of the EAA continue to be convinced that the MPP is a viable solution to deliver sustainably priced treatment – for both new fixed dose combinations and pediatric formulations,” reiterated David Deakin. “We therefore urge other companies to follow the example that BMS has set as soon as possible. In particular, we call on those currently in negotiations with the MPP, such as ViiV for dolutegravir and AbbVie for pediatrics, to speedily conclude their agreements, and those who are have not yet entered into negotiations, such as Johnson and Johnson, and Merck, to do so as soon as possible.”

The MPP negotiates with patent holders to share their HIV medicine patents with the Pool, and then licenses generic manufacturers to facilitate the production of affordable generic medicines well-adapted for use in resource-poor settings. UNAIDS estimates that there are 35.3 million people living with HIV, with 28.6 million now eligible for antiretroviral therapy.

For more information: contact Sara Speicher, sspeicher@e-alliance.ch, +44 7821 860 723

 

The Ecumenical Advocacy Alliance is a broad international network of churches and Christian organizations cooperating in advocacy on food and HIV and AIDS. The Alliance is based in Geneva, Switzerland. For more information, see http://www.e-alliance.ch/

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UNAIDS: It’s not Just about Pills. 11/12/2013

AJAN News

ICASACommunity-based approaches are essential to reach 14 million people in Africa who still don’t have access to life-saving antiretroviral treatment (ART), said UNAIDS Director Michel Sidibé.

In a compelling address during a UNAIDS session at ICASA on 9 November about scaling up treatment coverage, Sidibé made it clear that rollout was not just about distributing pills but about life, dignity and human rights. 

“We still have 14 million people waiting,” Sidibé told the high-level session that included the Global Fund to Fight AIDS, Malaria and TB and PEPFAR (President's Emergency Plan for AIDS Relief) on the panel. “We can’t afford to let them down. Access to treatment is a human right and not just a matter of giving pills to people.”

Sidibé said treatment had to reach people where they were – which is not in reality as obvious as it sounds. He urged key decision-makers to view AIDS treatment as a means of revolutionising the continent’s health systems and to turn to community models of care.

“It is critical to reach people not reached today by our services. We cannot end AIDS if we do not bring such people to the centre of our approach,” he said. “It’s not only an issue of treatment but of transforming our health approach, of seeing how we can use our community health workers to simplify things and reach people where they are.”

For Sidibé, the shift towards the community is imperative – otherwise “we’ll never reach the 14 million” – and must be matched by innovation in the technical sphere to produce user-friendly equipment. “We need to democratize access to tools, going for technology that will help us improve our approach by making sure communities can use it.”

The UNAIDS Director said reaching the goal of having 15 million people on ART by 2015 would avoid 1.4 million deaths, help to prevent 500,000 new infections and protect seven million children from becoming orphans.

These impressive gains mean that money spent on treatment is not being wasted: “Treatment is not just about giving pills but about restoring dignity. We are making sure we save lives. Treatment is not a cost for me, it is an investment, and we need to show this to our ministers of finance and our high-level decision makers. If we can avoid 1.4 million deaths, for me nothing can be more worthy than avoiding those unnecessary deaths.”

Taking the floor after Sidibé, Global Fund Executive Director Mark Dybel took a step away from an exclusive focus on treatment although he admitted it is hugely important. “We are not going to end the epidemic by just putting people on treatment,” he said. “It is part of the solution but not all of it.”

Looking on treatment as prevention, Dybel cited studies to cast doubt on the “real-life effectiveness” of ART as prevention. While initial research conducted among discordant couples reported a 96% reduction in transmission, other studies have revealed rates that are far lower.

“Uganda has universal access to treatment and increasing incidence rates,” said Dybel. “This doesn’t mean treatment is not effective but you cannot get to zero infections with treatment alone. And we have the data to prove it.”

AJAN representatives at ICASA who attended the session were enthusiastic about what they heard.

“Sidibé was very good, saying treatment is not just about taking pills, it is about keeping people alive, about restoring their dignity as – and this is my addition – human beings created by God,” said Kelly Michelo SJ, coordinator of the home-based care program of Chikuni in rural Zambia.

“We need a paradigm shift that addresses critical enablers and, in this way, we can reach more people where they are.”

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Trailblazing Move to Take HIV Treatment Out of Clinics. 2/12/2013

by Laura Lopez Gonzalez

Some of South Africa’s 2.4 million HIV patients will be able to get antiretroviral (ARV) outside of health clinics in a move the Department of Health hopes will help address stock outs.

 

Currently, many patients in the country queue monthly to pick up their ARVs but as part of its latest funding application to the international financing mechanism, The Global Fund to Fight AIDS, TB and Malaria, the country is planning to move treatment out of clinics and into patients’ homes, local libraries and maybe even their local chain clothing store, like PEP, in the next three years.

South Africa will be one of the first countries in the world to implement such a system.

According to South African National AIDS Council CEO Dr Fareed Abdullah, Deputy-Director General Dr Anban Pillay is already overseeing work into possible models.

“The Department of Health is busy designing a mechanism for providing ARVs through courier services in the community,” Abdullah said. “The good news is that we expect that service could become available to about 300,000 patients.”

Department of Health Spokesperson Joe Malia said community treatment models are just one way the department is looking to tackle the allegedly widespread stock outs affecting the country.

The Department of Health is likely to put out a call to invite proposals for multiple community models but will also be rolling out community adherence clubs nationally, Abdullah added.

Piloted by the international medical humanitarian, Medicines Sans Frontieres (MSF), these clubs were first developed in Khayelitsha.

As part of these clubs, stable, long-time ARV patients meet in the community – at someone’s house or a nearby library. A trained counsellor distributes a patient’s two-month ARV supply and does a quick check up of the patient. Unless counsellors pick up problems, patients see a clinician annually for a check up as well as routine blood tests

Dr Gilles Van Cutsem is MSF’s Medical Coordinator for South Africa and Lesotho. Van Cutsem says the organisation has welcomed a national rollout of the clubs, which were formally adopted by the Western Cape this year.  The Western Cape also approved four-month supplies of ARVs for use in the clubs ahead of December, to accommodate those travelling home to the Eastern Cape during the festive season.

More than 20 percent of all Cape Metro ARV patients are currently part of an ART Adherence Club, according to Van Cutsem. Research has shown that club members were more likely to stay in care and were almost 70 percent less likely to see spikes in their HIV blood levels.

But he cautioned that community models of treatment may not be an answer to stock outs.

“To run adherence clubs successfully, it’s essential to have a consistent supply of treatment,” he said. “The main challenge will be to fix on-going drug supply chain problems.”

Moving ARVs into patients’ homes or communities will also depend on the ability of government to roll out fixed dose ARVs. Without these, the ARV stocks will likely remain too bulky for counsellors or couriers to carry multiple orders at one time.

In just days, world leaders will meet in the US capital, Washington, DC, to decide the fate of one of The Global Fund, one of the world’s leading funders of HIV programmes.

South Africa has historically been one of only a handful of African countries that not only receives funding from The Global Fund but also contributes to it. While donors like France, South Korea and the United States have already signalled their support, South Africa’s potential contribution has yet to be announced.  – Health-e News Service

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Trailblazing Move to Take HIV Treatment Out of Clinics. 2/12/2013

by Laura Lopez Gonzalez

Some of South Africa’s 2.4 million HIV patients will be able to get antiretroviral (ARV) outside of health clinics in a move the Department of Health hopes will help address stock outs.

Currently, many patients in the country queue monthly to pick up their ARVs but as part of its latest funding application to the international financing mechanism, The Global Fund to Fight AIDS, TB and Malaria, the country is planning to move treatment out of clinics and into patients’ homes, local libraries and maybe even their local chain clothing store, like PEP, in the next three years.

South Africa will be one of the first countries in the world to implement such a system.

According to South African National AIDS Council CEO Dr Fareed Abdullah, Deputy-Director General Dr Anban Pillay is already overseeing work into possible models.

“The Department of Health is busy designing a mechanism for providing ARVs through courier services in the community,” Abdullah said. “The good news is that we expect that service could become available to about 300,000 patients.”

Department of Health Spokesperson Joe Malia said community treatment models are just one way the department is looking to tackle the allegedly widespread stock outs affecting the country.

The Department of Health is likely to put out a call to invite proposals for multiple community models but will also be rolling out community adherence clubs nationally, Abdullah added.

Piloted by the international medical humanitarian, Medicines Sans Frontieres (MSF), these clubs were first developed in Khayelitsha.

As part of these clubs, stable, long-time ARV patients meet in the community – at someone’s house or a nearby library. A trained counsellor distributes a patient’s two-month ARV supply and does a quick check up of the patient. Unless counsellors pick up problems, patients see a clinician annually for a check up as well as routine blood tests

Dr Gilles Van Cutsem is MSF’s Medical Coordinator for South Africa and Lesotho. Van Cutsem says the organisation has welcomed a national rollout of the clubs, which were formally adopted by the Western Cape this year.  The Western Cape also approved four-month supplies of ARVs for use in the clubs ahead of December, to accommodate those travelling home to the Eastern Cape during the festive season.

More than 20 percent of all Cape Metro ARV patients are currently part of an ART Adherence Club, according to Van Cutsem. Research has shown that club members were more likely to stay in care and were almost 70 percent less likely to see spikes in their HIV blood levels.

But he cautioned that community models of treatment may not be an answer to stock outs.

“To run adherence clubs successfully, it’s essential to have a consistent supply of treatment,” he said. “The main challenge will be to fix on-going drug supply chain problems.”

Moving ARVs into patients’ homes or communities will also depend on the ability of government to roll out fixed dose ARVs. Without these, the ARV stocks will likely remain too bulky for counsellors or couriers to carry multiple orders at one time.

In just days, world leaders will meet in the US capital, Washington, DC, to decide the fate of one of The Global Fund, one of the world’s leading funders of HIV programmes.

South Africa has historically been one of only a handful of African countries that not only receives funding from The Global Fund but also contributes to it. While donors like France, South Korea and the United States have already signalled their support, South Africa’s potential contribution has yet to be announced.  – Health-e News Service

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Earlier HIV Treatment Could Save South Africa Money. 6/11/2013

Starting HIV patients on antiretrovirals (ARV) earlier may save South Africa money in the short-term, but doctors caution such a move may risk patients.

In 2011, the nine-country HPTN 052 study found that starting HIV-positive people on ARVs earlier and at higher CD4 counts of between 350 and 550 reduced their risks of transmitting the virus by about 96 percent. It also bolstered a growing body of observational data that earlier treatment benefited HIV patients too, by keeping them healthier longer.

Based in part on the study, the World Health Organisation (WHO) issued 2013 guidelines recommending that countries start HIV patients on ARVs at a CD4 count of 500 or below instead of 350 or less.

The South Africa government has yet to move to earlier treatment, and cost is one of many concerns.

Now Harvard University researchers in the United States have released research showing that such a move may actually save South Africa money.

Using data collected in the HPTN 052 study, Harvard University Medical School professor Rochelle Walensky and a team of researchers projected the costs of earlier treatment in South Africa.

Published in The New England Journal of Medicine, Walensky’s study found that earlier treatment in South Africa would actually save the country money primarily by preventing illnesses like tuberculosis in people living with HIV. She added that the a projected decrease in new HIV infections also contributed to the move’s cost effectiveness.

“The prevention benefit of early ARV therapy cannot be overlooked and contributes also to improved life expectancy to (HIV-negative) partners and decreased costs over time,” she told Health-e.

But in the long run, early treatment is likely to cost the country about as much as treatment under the country’s current guidelines, because “patients will live much longer and take these effective medications for many years.”

In the past, these kinds of costing projections have played an important part in prompting the South African government to adopt international recommendations.

“While the WHO has provided … recommendations, most countries – including South Africa — have not yet begun to implement the guidelines, often citing cost and cost-effectiveness concerns,” she said. “We have now demonstrated that these concerns are most likely unfounded.”

But the move to earlier treatment is not just about the money, caution South African doctors.

In response to the WHO’s new guidelines, the Southern African HIV Clinicians Society acknowledged that there were scientifically proven benefits of early ARV treatment for pregnant mothers and those in relationships with HIV-negative people.

However, the body said that data regarding the potential benefit of earlier treatment for others living with HIV was still relatively weak.

In the meantime, moving to earlier treatment in South Africa might risk putting patients at an unnecessary increased risk of developing drug resistance and increased side effects as consequences of spending longer on treatment in their lifetimes.

This is especially true given the frequency of drug stock outs, according to Deputy Executive Director of the Wits Reproductive Health and HIV Centre Dr. Francois Venter.

“We have mass stock outs across the country – (fixing this) should be the priority, not expanding access further when we can’t cope with existing demand,” he told Health-e. “We should focus on getting our drug supply systems working well, before expanding access.”

He added that currently modelling regarding the cost effectiveness of early ARV initiation in South Africa has largely not factored in the risk of such treatment interruptions. – Health-e News Service.

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Single Dose Treatment Regimens Associated with Lower Pharmacy Costs, Fewer Hospitalisations and Lower Hospital Costs in the US 04/10/2013

 

Association between daily antiretroviral pill burden and treatment adherence, hospitalisation risk, and other healthcare utilisation and costs in a US medicaid population with HIV.

Cohen CJ, Meyers JL, Davis KL. BMJ Open. 2013 Aug 1;3(8). doi:pii: e003028. 10.1136/bmjopen-2013-003028.

Objectives:  Lower pill burden leads to improved antiretroviral therapy (ART) adherence among HIV patients. Simpler dosing regimens have not been widely explored in real-world populations. We retrospectively assessed ART adherence, all-cause hospitalisation risk and costs, and other healthcare utilisation and costs in Medicaid enrollees with HIV treated with ART as a once-daily single-tablet regimen (STR) or two or more pills per day (2+PPD).

Design:  Patients with an HIV diagnosis from 2005 to 2009 receiving complete ART (ie, two nucleoside/nucleotide reverse transcriptase inhibitors plus a third agent) for ≥60 days as STR or 2+PPD were selected and followed until the first of (1) discontinuation of the complete ART, (2) loss of enrolment or (3) end of database. Adherence was measured using the medication possession ratio. Monthly all-cause healthcare utilisation and costs were observed from regimen initiation until follow-up end.

Results:  Of the 7 381 patients who met inclusion criteria, 1 797 were treated with STR and 5 584 with 2+PPD. STR patients were significantly more likely to reach 95% adherence and had fewer hospitalisations than 2+PPD patients (both p<0.01). STR patients had mean (SD) total monthly costs of $2 959 ($4 962); 2+PPD patients had $3 544 ($5 811; p<0.001). Hospital costs accounted for 53.8% and pharmacy costs accounted for 32.5% of this difference. Multivariate analyses found that STR led to a 23% reduction in hospitalisations and a 17% reduction in overall healthcare costs. ART adherence appears to be a key mechanism mediating hospitalisation risk, as patients with ≥95% adherence (regardless of regimen type) had a lower hospitalisation rate compared with <95% adherence.

Conclusions:  While it was expected that STR patients would have lower pharmacy costs, we also found that STR patients had fewer hospitalisations and lower hospital costs than 2+PPD patients, resulting in significantly lower total healthcare costs for STR patients.

Abstract Full-text [free] access

Editor’s notes: This observational study using insurance claims of over seven thousand patients over three years looked at differences in adherence between patients taking a single tablet per day as compared to those prescribed ART treatment of more than a single tablet each day. Almost a quarter of the patients were on a single pill regimen. Adherence was assessed using the medication possession ratio which is a common proxy for medication adherence. This measures “the proportion of the ART-exposure period in which supply was maintained for all ART components comprising the regimen”. Though observational studies may be subject to numerous biases, they are the only approach to studying real world adherence. By showing in subgroup analysis that high and low adherers in each treatment group have similar hospitalization rates and health care costs, they are able to conclude that the key difference in outcomes is attributable to differences in adherence rates between the regimens. Further sub-group analyses address the various potential selection biases present. Authors found that not only were drug costs lower for the single dose regimen, but these were easier for patients to adhere to, which in turn leads to lower morbidity, hospitalization rates and health care costs.  Though this appears a win-win situation, there are only limited drug combinations available as single pill regimens at present; therefore, they are not always appropriate for all patients. This study provides an additional impetus for continued development of single pill regimens to increase their access to a broader range of patients and improve patient outcomes.

Northern America
United States of America
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Stronger Community Systems Vital to Scaling up HIV Treatment. 26/09/2013

The International HIV/AIDS Alliance welcomes the World Health Organisation’s (WHO) guidelines on the use of antiretroviral therapy (ART) for treating and preventing HIV infection which were launched at the 7th International AIDS Society conference on HIV Pathogenesis Treatment and Prevention in Kuala Lumpur today.

The new guidelines recommend that people living with HIV should be offered ART when their CD4 cell* count falls below 500 cells/mm3, compared with the current threshold of less than 350 cells/mm3. This change in the threshold means that people living with HIV can have access to ART much earlier. Starting treatment when the CD4 count is higher – and the immune system is stronger – has shown to slow clinical progression, reduce the chance of life-threatening conditions such as tuberculosis (TB), and reduce the risk of HIV transmission.

Dr Gitau Mburu, senior advisor on health systems and services at the Alliance, said “We are pleased to see the emphasis in the guidelines on earlier and inclusive access to safer ART delivered in a patient-centred manner. If implemented correctly, these guidelines have the potential to offer an earlier lifeline to millions more around the world.”

The recommendations also include offering treatment regardless of CD4 count (i.e. immediate treatment after HIV diagnosis) to pregnant women living with HIV, people living with HIV and TB or Hepatitis B, children under five years old living with HIV, and people in relationships where one partner is living with HIV and the other is not (serodiscordant couples).

Civil society consultation to inform the new guidelines

Between November and December 2012, the Global Network of People Living with HIV (GNP+) and the Alliance, in collaboration with WHO, conducted a civil society consultation in order to inform the above guidelines. Communities living with and most affected by HIV and civil society organisations supporting community action on AIDS were surveyed in-order to ensure that their values, preferences and recommendations were considered in the process of guideline development.  Respondents emphasised the need for meaningful community engagement at all levels once countries begin adapting and implementing the 2013 ART guidelines in order to be able to achieve global HIV targets.

Implementation challenges

Whilst the new guidelines are welcome, we do not underestimate the challenges ahead.  

Millions are still not getting the life-saving treatment they are entitled to and at the same time, there is a significant withdrawal of international aid from many of the middle-income countries with large HIV epidemics.

Anja Teltschik said “Whilst recent biomedical developments have proved the benefits of starting ART earlier, i.e. below 500 cells/mm3, both in terms of treatment and prevention, this comes at a time when HIV programmes face funding challenges which threaten universal access to HIV treatment and services.  In addition, social, structural and political barriers continue to hamper the HIV response that need to be addressed urgently to pave the way for greater effectiveness of interventions and inclusive access.”

To mitigate against these risks, GNP+, the Alliance and Dutch NGO, STOP AIDS NOW! are working together to develop a ‘Community Guide’ for use by networks, community-based organisations, and other civil society organisations supporting community action on AIDS.  The Guide aims to support communities to position themselves in discussions at regional and national levels about policy-making, programming, implementation and evaluation of programmes that use treatment.  Download our joint statement in response to the guidelines.

Access to treatment – what progress?

The rapid expansion of antiretroviral therapy is one of the most remarkable achievements in recent public health history. The scaling up of ART in low- and middle-income countries has transformed national HIV responses and generated broad-based health gains. According to UNAIDS, ART has saved 14 million life-years in low- and middle- income countries, including 9 million in sub-Saharan Africa, since 1995.

Before the new guidelines, close to 17 million people living with HIV in low- and middle-income countries were eligible for ART.  With the change in threshold, an estimated 26 million will now be eligible. However, in 2011 only 8 million people had access to the drugs.

There is still insufficient linkage between HIV testing and counselling, and a high drop-out of people enrolled in HIV care and treatment. There is an urgent need to improve retention rates. We know that community engagement has the potential to generate robust, sustainable demand for HIV testing and counselling and treatment services and to improve treatment adherence and other treatment-related outcomes. This is a programming priority for the Alliance in our global strategy, HIV, health and rights: sustaining community action.

* HIV most often infects CD4 cells which are in important part of the immune system. When someone is infected with HIV but has not started treatment, the number of CD4 cells they have goes down. This is a sign that the immune system is being weakened. The lower the CD4 cell count, the more likely the person will get sick.

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Integration of HIV Care into Primary Care Reduces Deaths in South African Trial. 10/9/2013

Carole Leach-Lemens, AIDSMap News 

Integrating HIV care into primary care can improve survival of people living with HIV who are in need of antiretroviral therapy (with CD4 counts of 350 cells/mm3 or less) in high-burden countries with task-shifting and decentralisation of care in place, researchers report in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.

Measurement of the effect of integration on survival in over 9000 people with CD4 counts at or under 350 cells/mm3, not yet on antiretroviral therapy (ART), in 31 clinics followed for 12 to18 months in Free State Province, South Africa showed a decreased risk of death in those clinics with high scores for integration, independent of other patient or clinic characteristics known to affect survival.

Every one point increase in total integration score was linked to a 3% decreased risk of death (HR 0.97; 95: CI: 0.95-1.00; p = 0.041) in this sub-study (a questionnaire) of a randomised controlled trial looking at the effects of task-shifting and decentralisation of care on patient outcomes in South Africa – the Streamlining of Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) trial.

This is of particular relevance since ART is currently being integrated into primary care in South Africa.

With an estimated seven million people having started ART in sub-Saharan Africa resulting in significant decreases in mortality the importance of attaining universal coverage has been recognised. Yet, close to half of those in need are still without treatment. 

Health infrastructure problems in sub-Saharan Africa led many countries at first to set up vertical (stand-alone) HIV care programmes with separate funding, staff and facilities.

Such programmes unable to reach all in need of ART in high-burden countries should be incorporated within existing health systems' programmes to both provide HIV care and strengthen these systems, the authors write.

Task-shifting has addressed the problem of healthcare worker shortage in many countries with good patient outcomes. Task-shifting alone, however, cannot resolve health systems' deficiencies or identify sustainable strategies integrating HIV care.

Integration, a broad concept, overlaps with that of decentralisation. In the absence of a clear definition, there is scant evidence showing integration improves patient outcomes, write the authors. As such, sustainable strategies are lacking.

A wide variety of programmes described as decentralisation or integration of HIV care have significantly improved access to care and include primary care-driven models, note the authors. Studies have reported on strategies to integrate HIV care into all primary care consultations. All have reported good outcomes but none, they stress, were conducted as clinical trials.

So the authors chose to look at the effect of integration of HIV care into primary care services on patient survival in a sub-study, using a questionnaire developed during the trial to answer two specific questions.

  1. Is there evidence that integrating HIV care into primary care services improves survival for patients with CD4 counts at or under 350 cells/mm3 and not on ART?
  2. If so, what level of integration of HIV care into primary care is important to improve patient survival?

Free State Province has an estimated adult HIV prevalence of 18.5% in a population of 2.8 million. In 2004, using a vertical approach to HIV care, the public sector ART programme began.

While 57 ART assessment and treatment clinics were in operation by mid-2007, most of the 222 primary care clinics could not offer on-site access to ART. Those on ART did well but only an estimated one in four people in need of ART were getting it. Fifty per cent of those awaiting ART died within a year.

The STRETCH trial began in 2007 to determine strategies to improve access to ART. All 31 ART assessment clinics in operation by the end of 2006 were randomised to 16 intervention and 15 control clinics. The two main interventions comprised 1) nurses starting and repeating ART prescriptions in uncomplicated cases with referral of complicated cases to doctors at treatment sites and 2) integrating elements of HIV care into primary care services so patients could access most of their care at primary care instead of the assessment clinic.

The questionnaire comprised questions on the number of staff and referring primary care clinics and 19 on integration of elements of HIV care.

Each question was scored: 0 for no integration, 1 for partial and 2 for full integration.

For each clinic five integration scores were determined as follows:

  • Total integration – total score for all 19 questions.
  • Pre-ART integration – on provision of HIV care by all nurses for patients not yet eligible for ART.
  • ART integration – on provision of HIV care for patients eligible for and on ART.
  • Internal integration – on provision of pre-ART and ART care within the ART clinic.
  • Mainstreaming HIV – on provision of pre-ART and ART care by nurses at referring primary care clinics.

Internal integration scores could be assessed for all 31 clinics, while the other scores could only be calculated for 23 clinics (13 intervention and 10 control) that still had primary care clinics referring patients for HIV care at the end of the trial. The other eight, all in rural areas, followed department of health policy to establish more ART clinics in rural areas.

In all 31 clinics there was a significant decrease in death for each increase in internal integration scores.

Hazard ratio analysis was repeated without adjusting for clinic characteristics to see whether components of integration made a difference to survival by affecting staff/patient ratios and improving access to rural clinics.

In the 23 clinics, for every one point increase in pre-ART integration there was a significant 8% decrease in death (HR:0.92; 95% CI: 0.85-0.99; p = 0.027); 5% for every one point increase in ART integration scores (HR:0.92; 95% CI: 0.93-0.98; p = 0.001) and 10% for every one point increase in mainstreaming HIV scores (HR:0.90; 95% CI: 0.83-0.97, p = 0.007) but no difference in death rates in the 31 clinics with changes in internal integration scores.

This would suggest that internal integration in all 31 clinics, with a larger percentage of rural clinics, has a significant impact on survival when HIV care is available in all primary care clinics so improving patient/staff ratios, note the authors.

The potential means by which integration of HIV care into primary care improved survival included improved access to care, decreased stigma and improved confidentiality, continuity and comprehensiveness of care, the authors write.

Another potential mechanism, they add, is improved quality of care with evidence from the STRETCH trial showing improved TB case detection, weight gain and increase in CD4 counts in intervention clinic patients.

Strengths include quantifying integration of different elements of HIV care and the levels at which integration took place with a tool, validated within a randomised, controlled trial.

Patient survival was monitored by linkage to the national death register.

STRETCH showed a significant difference in survival only among patients with CD4 counts between 200 and 350. This sub-study showed that one intervention – integration of HIV care into primary care clinics – was associated with improved survival of all patients with CD4 counts at or under 350.

The authors conclude “these results…of practical importance to policy makers in high burden countries…suggest that pre-ART and ART care be provided as part of the package of care provided in all primary care services and efforts be made to integrate HIV care into all consultations within primary care.”

Reference

Uebel KE et al. Integration of HIV care into primary care in South Africa: effect on survival of patients needing antiretroviral treatment. Advance online edition J Acquir Immun Defic, doi: 10.1097/QAI.0b013e318291cd08, 2013.

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CD4 Cell Count at Time of Entry to HIV Care did not Increase Significantly Between 1992 and 2011 - 21/08/2013

Major implications for debates about treatment as prevention and when to start therapy

By Michael Carter of namaidsmap
 

The average CD4 cell count of people newly entering HIV care in resource-rich countries did not increase meaningfully between 1992 and 2011, results of a systematic review published in Clinical Infectious Diseases show.

“Many people with HIV infection in high income-countries present late for care and may start treatment even later,” said Professor Joep Lange of the Netherlands in an accompanying editorial. “The finding that so little has changed with regard to time of presentation to HIV care in a period that saw dramatic improvements in HIV treatment and monitoring is astonishing.”

CD4 cell count is used to monitor the immune status of people with HIV. Late diagnosis is defined as presentation with a CD4 cell count below 350 cells/mm3, the minimum threshold for starting antiretroviral therapy. Diagnosis is very late if CD4 cell count is below 200 cells/mm3, therefore showing a high risk of AIDS-related illnesses.

It is well known that the timing of HIV diagnosis can have profound individual and public health consequences. Late diagnosis is a factor underlying much of the HIV-related illness and death that continues to be seen in resource-rich countries. In addition, there's evidence that undiagnosed individuals are responsible for a disproportionately large number of new HIV transmissions. Late diagnosis is also expensive to healthcare systems.

A team of investigators from the United States and United Kingdom wanted to see if the immune status of adults newly entering HIV care in richer countries changed between 1992 and 2011. They therefore conducted a systematic review of studies reporting on CD4 cell count at the time of entry to care.

“To our knowledge,” comment the authors, “no systematic review has assessed temporal trends in the clinical status of persons presenting to HIV care across cohorts in developed countries.”

During the twenty-year period of the study, there were major advances in HIV diagnostics, monitoring, care and treatment, especially the introduction of effective, tolerable and easy-to-take antiretroviral combinations. 

The investigators conducted a database search in late 2011, identifying peer-reviewed studies published between 2000 and 2011 that reported on the CD4 cell count of people newly entering HIV care.

A total of 44 studies with 169,000 patients met their inclusion criteria. Most of these involved patient cohorts in the United States (18) or the United Kingdom (11).

The mean CD4 cell count of people entering care in 1992 was 307 cells/mm3. There was an estimated increase of 1.5 cells/mm3 each year, and in 2011 the mean CD4 cell count of people newly entering care was 336 cells/mm3. These findings remained essentially unchanged in a series of sensitivity analyses.

The investigators also showed there were only minimal changes in the proportion of people presenting late or very late. In each case there was a reduction of only 0.1% each year.

The authors believe their findings have significance for debates about the use of antiretroviral treatment as prevention: “The promise of such approaches is unlikely to be realized unless improvements in timeliness of HIV diagnosis and presentation for care are achieved, dramatically altering the trajectory of the temporal trends observed over the past 2 decades.”

There is also controversy about whether HIV therapy should be started at a CD4 cell count of 350 cells/mm3 or the higher level of 500 cells/mm3. “Our study findings indicate that the considerations of when to start may be immaterial for the majority of patients who continue to enter care below any of the recommended treatment thresholds,” comment the authors.

They conclude: “New and innovative strategies to identify persons earlier in the course of their HIV infection and link them promptly with medical care are clearly necessary and desperately needed to fully realize the individual and public health benefits afforded by contemporary HIV treatment.”

Professor Lange echoes this conclusion in his editorial. “We need to increase HIV testing…we need to direct our efforts primarily at those populations most at risk of HIV infection, and repeatedly test those found to be HIV negative,” writes Lange. “In those found to be infected, we need to spell out clearly, and again and again, the importance of early treatment for their own health, beside that of minimizing the risk of onward HIV transmission.”

Lesko CR et al. A systematic review and meta-regression of temporal trends in adult CD4+ cell count at presentation to HIV care, 1992-2011. Clin Infect Dis, doi: 10.1093/cid/cit421, 2013.

Lange JMA Under the spell of the Red Queen. Clin Infect Dis, doi: 10.1093/cid/cit425, 2013.

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Compulsion versus Compassion: HIV Treatment for Women and Children. 8/7/2013

Alice Welbourn and Louise Binder consider whether the new World Health Organisation treatment guidelines for women and children living with HIV may result in more abuse and harm

50.50 inclusive democracy

New comprehensive treatment guidelines for people with HIV have just been launched by WHO at the international HIV pathogenesis conference, to a mixed response. These include revised treatment guidelines for women with HIV, and also for children with HIV.

The new treatment guidelines recommend that all children with HIV under 5, regardless of their actual health condition, be given anti-retroviral medication (ARVs). We have written before on opendemocracy 50.50  about the challenges of WHO and UNICEF wanting to put all women with HIV on treatment for life (known euphemistically as Option B+) and our concerns about the double-edged sword of “treatment as prevention” for women. Here we outline why blanket treatment for all children with HIV under 5 is of concern to us.

Whilst no-one is more anxious to keep children with HIV alive, healthy and happy than their own mothers, there has been extraordinarily little consultation with women living with HIV in this guidelines development process.  As anyone with young children knows, trying to get medication into a child can be an exercise in highly skilled negotiation. One would assume it might be useful therefore to consult the experts. Yet none of the key women living with HIV who are well-known women’s rights advocates in Africa, who are our colleagues, when we asked them earlier this year, had heard anything about the proposed guidelines changes.

As one of our colleagues, Martha Tholanah, a long-standing activist from Zimbabwe put it recently:

“I have been convinced I am missing something in all the debates as they have evolved over the best approaches for HIV-positive women, child-bearing and feeding options. With the advent of so much research and the emphasis on evidence-based approaches, it still seems as if women living with HIV cannot have the benefit of such informed public health approaches. All of a sudden WHO is launching new guidelines which appear not to be backed by evidence.  It was not easy getting to where I am today, with a daughter who turned out HIV-negative against all odds. A little over ten years ago, I was faced with a new diagnosis of HIV, and four weeks later, whilst still getting my head around that, I realized that I was pregnant. The medical profession at that time did not give me much confidence in the answers I needed in order to assist my decision-making. It seems ten years later, there is no political will to provide women who have to live with the consequences of the guidelines that we get from the experts, with enough information and support. It feels like, as HIV-positive women, we are being force-fed these guidelines. I have not heard of any consultations with the women who have to live with this. We know public health programs will be quick to adopt the guidelines wholesale. There is need to re-consider this action, and listen to the experts in lived realities – the HIV-positive women.”

So what are our concerns about this medication?

Firstly, adherence. ARVs are for life and you have to take them religiously not to build up resistance. So starting them has to involve huge commitment by all concerned. A recent powerful film from Malawi demonstrates how women with HIV face violence from their partners for even accessing their own ARVs from hospital. How then, given the widespread experiences of violence in healthcare settings that we know women also experience, do we expect women to risk more violence by seeking treatment for their children also? Furthermore, the liquid ARVs currently available for children need refrigerated storage. Yet there is no plan to roll out fridges to women across Africa.  It also tastes horrible and children spit it out. If they take too much they may be sick. So it is nigh impossible to tell if they are getting the right dose. If not, they will build resistance to the drug. If you develop resistance to ARVs in the UK there are second or third-line alternatives available. These are not widely available in Africa.

What about adequate food and water supplies? The guidelines highlight the importance of food in HIV care. Yet there is no parallel plan to scale up food and water security.

In the clinics themselves, the guidelines also highlight the importance of actually ensuring medicines keep arriving there. This is also a serious problem since interruption of medications – which is still widespread - also leads to resistance.

Most healthcare providers have not been adequately trained how to respect women’s own rights regarding their HIV, so they have minimal ability to support the women to provide these treatments to young children. The staff are also often overworked, often dealing with the secret of HIV in their own lives and do not have the time to assist women in a manner that encourages women and their children to continue to attend the clinic for care and treatment.

As with other aspects of these new guidelines, the scientific trials to date have also not supported the proposed guidelines.  There is no strong evidence yet that prolonged treatment on antiretrovirals in their formative years does not have an impact on bone and other growth factors in children as they become adolescents.

For all these reasons we have asked WHO and UNICEF why they are putting the cart before the horse in launching these guidelines before all these practical issues are addressed first. We have no doubt that they have done so with good intent. However our repeated experiences over the years are that when WHO issues guidelines, country programmes view them as the rulebook, and it’s women who get the blame if they don’t obey them.

There are also wider national and global health and societal issues at play here. Why, for instance, is there such a drive for “best guesses” over the evidence base? Why is there an ongoing reluctance, nay resistance, to acknowledge complexity, an inability to embrace the holistic realities of the world we inhabit, to involve as central those people who know most about an issue – i.e. those who are most deeply and personally affected by it? Why is there a continued rush to produce numbers when we all know that it’s the quality of an intervention which is the key to whether it actually succeeds or not, not the quantity of boxes ticked. To paraphrase Chris Mowles, institutions might be hitting the target, but often miss the point. For instance, we hear from Uganda that women are throwing away their ARVs as soon as they have stepped outside the hospital compound, for fear of reprisals at home. One boy recently stopped taking his medication because he didn’t want to be spotted by his school friends at the clinic. The clinic staff shouted at him for being so stubborn. So whilst the hospital records show many new uptakes of ARVs, our own sources reveal different narratives.

A recent conference in Southern France attended by over 500 healthcare professionals convened to address compassion in healthcare. It was an uplifting and enriching experience as we learnt of the hugely positive impact of approaching healthcare from a positive, collaborative holistic and inclusive approach. As we in the UK learn and grow from the Francis report and think about “intelligent kindness” in healthcare, we hope so much that compassion in UN global HIV care policy and practice might also be an imminent – and immanent - reality.

Read more articles in openDemocracy 5050's seriesAIDS, Gender and Human Rights

 

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Management of Age-Related Conditions is 'the Future of HIV Care', says IAS Conference Keynote Speaker. 1/7/2013

Liz Highleyman
 
Steven Deeks of the University of California San Francisco gives the keynote address at IAS 2013. Photo ©International AIDS Society/Marcus Rose/Workers' Photos
 

Other diseases are becoming far more important than AIDS for people with HIV who have consistent access and good response to antiretroviral treatment, and management of age-related comorbidities will become an increasingly important aspect of HIV medicine worldwide in the coming years, Steven Deeks argued in his keynote address yesterday at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) in Kuala Lumpur.

Deeks, from the University of California at San Francisco, has done extensive research on both ageing with HIV and cure-related strategies. Preceding the conference, he co-chaired a two-day Towards an HIV cure symposium with IAS president Françoise Barré-Sinoussi and Sharon Lewin from Monash University.

Among people living with HIV who are on effective antiretroviral therapy, the virus is kept under control, the immune system works pretty well and AIDS-related conditions are uncommon, Deeks said. "For people with drug-susceptible virus, who are motivated to take the drugs, and who have lifelong access to therapy, AIDS is no longer the problem." Instead, he explained, "HIV is looking a lot like other chronic diseases," characterised by persistent low-level immune activation and inflammation.

Several studies have shown that HIV independently confers an excess risk for cardiovascular disease and other non-AIDS conditions. A large US veterans cohort study that compared HIV-positive and -negative people, matched for age and other factors, found that people with HIV had about a 1.5-fold higher rate of heart disease – about the same excess risk associated with having diabetes. Effects of a similar size have been seen for bone loss, neurological impairment, kidney disease and certain types of cancer, Deeks noted.

Another study found that people living with HIV who are in their fifties have as many comorbidities, on average, as HIV-negative people 10 or 15 years older. "It looks like [HIV] adds a decade in terms of age-associated conditions," he said.

People with treated HIV have increased levels of multiple markers of inflammation. And these markers – especially interleukin 6 and D-dimer – predict excess risk of morbidity and mortality.

"If we venture out of the HIV world into rheumatology, cardiology and especially geriatrics, similar observations are made," Deeks continued. "Chronic inflammation is at least predictive – and probably causal – of comorbidities in study after study."

Heart attacks and the like are uncommon at age 40 to 50, so HIV has not yet had a major effect on absolute numbers, but is likely to do so as people age, he warned. "While most people with HIV are young now, as people on therapy get older – into their sixties, seventies and eighties – all these other diseases could add up to problems."

"I spend my time in the clinic talking about exercise, management of lipids, a Mediterranean diet, and so forth...We should all be helping our patients in their forties and fifties live to their seventies and eighties, so they're around for a cure." Steven Deeks

Furthermore, these conditions – mostly studied so far in the US and Europe – "are now playing out in developing world," Deeks said. "In Africans we're seeing a higher number of comorbidities even though the population is younger. The same thing that's happening in the US is likely happening on a global level." These excess comorbidities and the shift to chronic disease management could overburden already stretched healthcare systems.

But fortunately, Deeks continued, we can do something about it.

We know a lot about mechanisms of inflammation, why inflammation might cause disease and targets for potential therapies, he said. There are multiple drugs in the pipeline to try to reverse the process, as well as increasing evidence that starting antiretroviral treatment early rather than late may help prevent long-term residual inflammation (now being investigated in the START study).

Now that HIV is a chronic disease, Deeks argued, "we need to switch our focus from acute to chronic care, which requires a whole new set of skills and changes in the healthcare system."

Ultimately, he concluded, the various problems associated with chronic HIV disease – excess inflammation, heart disease, overburdened health systems, not being able to afford lifelong therapy – "could all be addressed by a cure."

"There's a tremendous amount of excitement and a bit of optimism that we're making enough progress that eventually we'll be able to cure the disease," Deeks continued. "But there are also substantial barriers to curing HIV infection – and some of them may be insurmountable."

Making an analogy with the development of antiretroviral drugs, he suggested that cure research is where antiretroviral therapy research was in the late 1980s, when we were learning about pathogenesis, how to measure HIV and beginning to identify potential targets to go after the virus.

Today we are trying to measure residual HIV in long-term treated people and have seen that certain agents can affect the biology of the virus. But "going after free virus [in the blood] was a lot easier than virus hidden in cells," he emphasised. "We have to find some ways to get in there without harming the patient."

The Towards an HIV cure meeting featured a lot of cutting-edge research, some of which will be presented during the week at the main IAS conference. Researchers will talk more about the case report of a baby in Mississippi, presented at this year's Conference on Retroviruses and Opportunistic Infections (CROI), which Deeks thinks "represents a clear-cut cure". There will be late-breaker presentations on allogeneic stem cell transplantation and small molecules that can "upset the steady state" of the viral reservoir.

"My geriatrician [colleagues] say if you want patients to be playing tennis in their 70s, you need to be dealing with that in their forties," Deeks said. "I spend my time in the clinic talking about exercise, management of lipids, a Mediterranean diet, and so forth...We should all be helping our patients in their forties and fifties live to their seventies and eighties, so they're around for a cure."

Reference

Deeks S Keynote address. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. www.ias2013.org.

Video and presentation slides from the opening session are available on the IAS website: http://pag.ias2013.org/session.aspx?s=64

NAM’s IAS 2013 bulletins have been made possible thanks to support from Bristol-Myers Squibb. NAM's wider conference news reporting services have been supported by Boehringer Ingelheim and Janssen.

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WHO Issues New HIV Recommendations Calling for Earlier Treatment. 30/6/2013

Earlier, safer and simpler antiretroviral therapy can push the HIV epidemic into irreversible decline

News release

New HIV treatment guidelines by WHO recommend offering antiretroviral therapy (ART) earlier. Recent evidence indicates that earlier ART will help people with HIV to live longer, healthier lives, and substantially reduce the risk of transmitting HIV to others. The move could avert an additional 3 million deaths and prevent 3.5 million more new HIV infections between now and 2025.

The new recommendations are presented in WHO’s "Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection", as new data reveal a total of 9.7 million people were taking these lifesaving drugs at the end of 2012.

“These guidelines represent another leap ahead in a trend of ever-higher goals and ever-greater achievements,” says WHO Director-General Dr Margaret Chan. “With nearly 10 million people now on antiretroviral therapy, we see that such prospects – unthinkable just a few years ago – can now fuel the momentum needed to push the HIV epidemic into irreversible decline.”

Call to initiate treatment at 500 CD4 cells/mm³ or less

The new recommendations encourage all countries to initiate treatment in adults living with HIV when their CD4 cell count falls to 500 cells/mm³ or less – when their immune systems are still strong. The previous WHO recommendation, set in 2010, was to offer treatment at 350 CD4 cells/mm³ or less. 90% of all countries have adopted the 2010 recommendation. A few, such as Algeria, Argentina and Brazil, are already offering treatment at 500 cells/mm3.

WHO has based its recommendation on evidence that treating people with HIV earlier, with safe, affordable, and easier-to-manage medicines can both keep them healthy and lower the amount of virus in the blood, which reduces the risk of passing it to someone else. If countries can integrate these changes within their national HIV policies, and back them up with the necessary resources, they will see significant health benefits at the public health and individual level, the report notes.

Further recommendations

The new recommendations also include providing antiretroviral therapy - irrespective of their CD4 count - to all children with HIV under 5 years of age, all pregnant and breastfeeding women with HIV, and to all HIV-positive partners where one partner in the relationship is uninfected. The Organization continues to recommend that all people with HIV with active tuberculosis or with hepatitis B disease receive antiretroviral therapy.

Another new recommendation is to offer all adults starting to take ART the same daily single fixed-dose combination pill. This combination is easier to take and safer than alternative combinations previously recommended and can be used in adults, pregnant women, adolescents and older children.

“Advances like these allow children and pregnant women to access treatment earlier and more safely, and move us closer to our goal of an AIDS-free generation,” said UNICEF Executive Director, Anthony Lake. “Now, we must accelerate our efforts, investing in innovations that allow us to test new born babies faster and giving them the appropriate treatment so that they enjoy the best possible start in life.”

The Organization is further encouraging countries to enhance the ways they deliver HIV services, for example by linking them more closely with other health services, such as those for tuberculosis, maternal and child health, sexual and reproductive health, and treatment for drug dependence.

“The new WHO guidelines are very timely in view of the rapid progress we have made in expanding programmes for prevention and treatment,” says Dr Mark Dybul, Executive Director of the Global Fund to Fight AIDS, Tuberculosis and Malaria. “This is an example of how the Global Fund and the WHO work together to support countries as we move towards removing HIV as a threat to public health." Since its creation in 2002, the Global Fund has supported more than 1,000 programmes in 151 countries, providing HIV treatment for 4.2 million people.

Challenges remain

Challenges still remain. Alongside the new treatment guidelines, a treatment progress update by WHO, UNAIDS, UNICEF identified areas in need of attention.

While the number of all eligible children on ART has increased by 10% between 2011 and 2012, this is still too slow compared to the 20% increase in adults. A further complication is that many key populations such as people who inject drugs, men who have sex with men, transgender people and sex workers, continue to face legal and cultural barriers that prevent them getting treatment that otherwise would be more easily available. Another factor that needs to be addressed is the significant proportion of people who, for many reasons, ‘drop out’ of treatment.

Data reinforces feasibility of recommendations

Despite this, the Global update on HIV treatment: results, impact and opportunities contains encouraging data that reinforces the feasibility of the new WHO recommendation on earlier ART, which would expand the global number of people eligible for antiretroviral therapy to 26 million.

Between 2011 and 2012, the largest acceleration ever of people enrolled on ART was achieved, with an extra 1.6 million people benefitting from antiretroviral therapy, increasing the total to 9.7 million people. Furthermore, increased coverage of treatment occurred in every region of the world, with Africa leading. Four out of 5 people who started treatment in 2012 were living in sub-Saharan Africa.

“Today nearly 10 million people have access to lifesaving treatment. This is a true development triumph,” says Michel Sidibé, Executive Director of the Joint United Nations Programme on HIV/AIDS (UNAIDS). “But we now have a new challenge - ensuring that all 26 million people eligible for treatment have access - not one person less. Any new HIV infection or AIDS-related death due to lack of access to antiretroviral therapy is unacceptable.”

Today’s recommendations were released by WHO on the opening day of the International AIDS Society 2013 conference in Kuala Lumpur. Among those endorsing the recommendations at the launch were representatives from countries, where such earlier ART intervention is already national policy, along with development agencies who are providing technical and financial support.

The International AIDS Society conference is held every two years and attracts leading scientists, clinicians, public health experts and community leaders to examine the latest developments in HIV-related research, and to explore how scientific advances can inform the global response to HIV/AIDS.

Note to editors:

The recommended treatment is now a combination of three antiretroviral drugs: tenofovir and lamivudine (or emtricitabine) and efavirenz, as a single pill, given once daily.

For more information please contact:

Mr Glenn Thomas
Communications Officer, WHO
Telephone: +41 22 791 3983
Mobile: +41 79 509 0677
E-mail: thomasg@who.int

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Study: Earlier HIV Treatment Means Drop in Early Death Rates. 17/6/2013

Findings highlight critical role of earlier treatment, support value of policies adopting earlier treatment guidelines

Science Speaks: HIV & TB News
By Antigone Barton

 

An analysis of data from all adults in a rural South Africa HIV program over the course of eight years has shown that after guidelines widened eligibility for antiretroviral treatment, death rates within the first three months of treatment dropped.

Lessells

Richard Lessells

The findings show results from World Health Organization 2010 guidelines for earlier initiation of patients on HIV-fighting medicine, and may encourage more countries to adopt policies for earlier initiation, study author Richard Lessells, of the Africa Centre for Health and Population Studies said. While conclusions from the findings can’t be projected to the results of expected continued eligibility expansions, “it is likely” that early death rates will continue to decline as the wait to begin treatment diminishes, he allowed.

The study  looked at data at a KwaZulu-Natal program beginning in 2004, when eligibility for antiretroviral treatment for adults in the program was tied to an immune cell count under 200, continuing through April 2010 when it was expanded to include pregnant women and people with active tuberculosis with immune cell counts of 350 or under, and after August 2011, when eligibility was expanded again to include all people with immune cell counts under 350.

More than 19,000 people started taking antiretroviral medicine to treat their HIV through the Hlabisa HIV Treatment and Care Programme, at 17 clinics and one hospital in Northern KwaZulu-Natalthe during the time researchers examined. During the first six years patients’ median immune cell count ranged from 110 to 120 at the time they started treatment. The median count rose to 145 after eligibility expanded, and then again, to 199 after all patients with the higher immune cell counts became eligible. Deaths during the first three months of starting treatment — many because patients were already succumbing to tuberculosis or other opportunistic infections — accounted for nearly 60 percent of the deaths over the years covered by the study. During those eight years,  875 people died within three months of starting treatment. But the early death rate dropped by 46 percent from 2011 to 2012. At the same time, the immune systems of people enrolling in the program, being diagnosed and tested for the first time were less damaged, with nearly half of the adults having immune cell counts of 350 and higher, indicating, at least in part, a higher motivation across the community to get tested, with a greater likelihood of receiving treatment, Lessells said.

The study took place in the area of South Africa where research recently showed that accelerated treatment coverage to be associated with increased life expectancy and lower risk of HIV acquisition on a community wide basis. Still, research also conducted by the Africa Centre for Health and Population Studies and others in the area has also shown that as health systems extend HIV treatment to greater numbers of people, retention in care is increasingly challenged.

“It really presses home though the focus is still getting people on treatment,” Lessells said, “At the same time we need to focus on quality of care and retention.”

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Longer Life Span in South Africans Starting ART With Over 200 CD4s 14/05/2013

International Aids Society: Mark Mascolini

Life expectancy in South Africans starting antiretroviral therapy (ART) with a CD4 count above 200 cells/µL is 70% to 86% of that in HIV-negative adults of the same age and sex and much longer than expected life spans in people starting ART with fewer than 50 cells/µL, according to results of a six-cohort modeling study.

ART has been available in low- and middle-income countries for a decade or more, but little is known about life expectancy in populations starting ART in these countries. To address this question. Southern Africa IeDEA collaborators analyzed data from six ART programs in South Africa’s Western Cape, Gauteng, and KwaZulu-Natal provinces between 2001 and 2010.

The IeDEA team estimated mortality by linking patient records to the national population register and used relative survival models to estimate excess mortality attributable to HIV by age for different pretreatment CD4 counts and different ART durations.

Among 37,740 adults who started ART, 2066 had a recorded death. Among 16,250 people who dropped out of care, the investigators identified another 2947 deaths in the population register. When the IeDEA researchers fed these data into their models, they found an overall mortality of 83.2 deaths per 1000 person-years, meaning about 8 in 100 people starting ART died every year. Mortality was much higher in men (99.8 per 1000 person-years) than in women (72.6 per 1000 person-years).

Age when ART began proved the most significant factor in determining life expectancy. Among men average life expectancy was 27.6 additional years for those starting ART at age 20 and 10.1 additional years for those starting at age 60. Corresponding estimates in women were 36.8 years and 14.4 years.

CD4 count when ART began had a strong impact on life expectancy compared with HIV-negative people. Among people starting ART with a CD4 count at or above 200 cells/µL, life expectancies lay between 70% and 86% of those in HIV-negative adults of the same age and sex. In contrast, people starting ART with a CD4 count below 50 cells/µL had life expectancies between 48% and 61% of those of HIV-negative adults.

Among people who survived the first 24 months of ART, life expectancies were 15% to 20% higher than in people the same age who had just started ART.

The IeDEA team cautions that their analysis is limited by lack of mortality data at longer durations. With this caveat in mind, they believe their findings “demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well.”

“Although these results are encouraging,” the editors of PLoS Medicine add, “this study highlights that health services must overcome major challenges, such as dealing with late diagnosis, low uptake of CD4 testing, loss from pre-ART care, and delayed ART initiation, if near-normal life expectancies are to be achieved for the majority of HIV-positive South Africans.”

Source: Leigh F. Johnson, Joel Mossong, Rob E. Dorrington, Michael Schomaker, Christopher J. Hoffmann, Olivia Keiser, Matthew P. Fox, Robin Wood, Hans Prozesky, Janet Giddy, Daniela Belen Garone, Morna Cornell, Matthias Egger, Andrew Boulle, for the International Epidemiologic Databases to Evaluate AIDS. Southern Africa (IeDEA-SA) Collaboration. Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies. PLoS Medicine. 2013; 10: e1001418.

 

Complete article provided by PLoS Medicine, an open-access journal

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AHF Marks Milestone of Testing More Than 1 Million People Worldwide for HIV in 2012

AIDS Healthcare Foundation, the largest global AIDS organization, surpassed a notable milestone in 2012 by testing more than one million individuals around the world for HIV -- those who tested positive for the virus at testing actions on four continents around the globe were immediately linked to treatment and care.

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Clockwise: A testing event on World AIDS Day 2012 (December 1, 2012) in Umlazi, South Africa • Argentina - one of AHF's newest partner countries - held its first AHF-supported testing event on World AIDS Day 2012 (December 1, 2012) in the town of Rosario, where AHF Argentina set a new Guinness World Record for most number of people tested for HIV in one city in one day by testing 3,733 people in 8 hours • A 2012 testing action on World AIDS Day 2012 (December 1, 2012) in Chongqing, China.

 

Routine HIV testing has long been seen as the starting point to stopping the global HIV/AIDS epidemic, and AIDS Healthcare Foundation (AHF), the largest global AIDS organization, has worked tirelessly toward the goal of "testing millions" and linking those who test positive for HIV to care. In 2012, with AHF-supported clinics and healthcare centers operating in 28 countries on four continents in conjunction with important partnerships with local non-government organizations (NGOs) and health ministries, the Foundation has tested more than one million individuals around the world in a single year.

 

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Through testing events and initiatives in Asia, Africa, Latin America, Europe, and the North America, AHF tested 1,061,865 people. Of those people, 43,981 tested positive for HIV and were immediately linked to treatment and care. This is an ambitious leap from previous years' testing totals -- 699,512 people were tested in 2011, and 513,768 learned their status in 2010 -- which is indicative of the emphasis AHF has placed on testing as the gateway to treatment and lifesaving knowledge about protecting oneself and one's partners.

 

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Forty-nine percent of those who got tested through AHF in 2012 were women, nearly matching the number of men who accounted for the other 51% of those tested. Of those tested, a higher rate of HIV-positivity was found in the women, who accounted for 54% of the total. Men accounted for 46% of the HIV-positive results. The majorities of both the people getting tested and those testing positive for HIV fell within the age range of 21-30 years old.

 

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Uganda saw the largest number of people being tested in 2012 with nearly 300,000 people learning their HIV status, where AHF opened its newest healthcare center outside of the U.S. in January 2013. Of those people, 5.08% learned they were positive for HIV and were linked to care. The highest rates of positivity were found in Zambia (10.48% of those tested), Swaziland (13.13% of testers), and South Africa, where 17.34% of the people who took an HIV test through AHF tested positive for the virus. South Africa carries the largest global AIDS burden with approximately 5.6 million people living with HIV in the country. Despite this clear need for accessible antiretroviral treatment (ART), funding cuts to the President's Emergency Plan For AIDS Relief (PEPFAR) in 2012 have threatened the operation of at least two clinics there.

 

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With year-round global testing in cities scattered from Russia to Rwanda and Kathmandu to Mexico City, AHF is on track to test more than 1.5 million people in 2013. Knowing one's HIV status allows those who are living with the virus to become aware of it as early as possible and begin lifesaving medical treatment at the point in the disease where the medication would have its most potent effect. Additionally, being aware of one's status allows for open and honest dialogue between sexual partners to minimize the risk of passing HIV unwittingly. Most importantly, because AHF has clinicians and counselors directly linked to their testing campaigns around the world, people who do learn that they are HIV-positive will experience the hope that access to treatment brings. They are immediately offered vital emotional counseling and are educated right away about their treatment options and how to live a full life with this manageable condition. Because AHF supports clinics in 28 countries on four continents, clients are given options that will make it easy for them to stay on their treatment regimen, which is highly important in controlling HIV and living well.

 

“Wherever we do testing the world over, AHF has always found the same truth: People want to take care of themselves, their families and their partners. When we offer free HIV tests to the community in a convenient and accessible way—whether in South Florida or South Africa--community members come forward because they know how urgent it is to get tested and know their status," said AHF President Michael Weinstein. "We will continue to provide easy access to accurate, speedy testing around the world so millions more can know their status because it is the first step in breaking the chain of infection and halting the epidemic."

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HIV Drug Resistance Test to Slash Costs by 80 Percent

CAPE TOWN, 10 April 2013 (allAfrica) - Researchers in South Africa have developed a low-cost tool to test for HIV drug resistance, potentially opening the door to improved treatment for users of antiretroviral drugs (ARVs).

Source: SciDev.Net and Safaids

The researchers, based at the University of Western Cape's South African National Bioinformatics Institute (SANBI), have developed a computer-based tool - Seq2Res - that vastly reduces the costs and time involved in analysing data about viral DNA compared to conventional methods.

Simon Travers, bioinformatics associate professor and project leader at SANBI, says the tool allows HIV drug resistance testing of samples from almost 50 patients pooled together, which makes it significantly cheaper. Conventional method can only assess one patient's data at a time.

"Our tool makes this analysis easy," Travers tells SciDev.Net.  It is also expected to be five times cheaper than the average conventional testing system.

Travers says that the tool offers a more sensitive HIV drug resistance test by identifying drug resistant viral variants circulating at low levels in individuals. Viral sequences are listed and compared to a reference virus to identify the presence of mutations that are known to cause drug resistance.

"The software will allow for more manageable processing and interpretation of sequence data obtained using next generation sequencing platforms for HIV resistance surveillance," Gillian Hunt, a researcher from South Africa's National Institute for Communicable Diseases, tells SciDev.Net.

Travers says the new tool will enable researchers and clinicians to easily process their drug resistance testing data without needing expert bioinformatics assistance.  The data will be collected and stored in a large database, which will be accessible to researchers at no charge as a service to the academic research community.

Travers explains that the researchers are three months into the development of the web application and that tests will start by end of June, with a final roll-out of the Seq2Res tool set for September this year.

The tool currently used in the research laboratory at SANBI is being developed into a web-based application with US$120,000 of funding from the South African government's Department of Science and Technology (DST).

The tool is designed to be user-friendly, with no specialised training required: any clinician or research scientist who understands HIV drug resistance should be able to use it, Travers says.

The only tool required by the user is access to next-generation sequencing facilities to generate the input data, he adds. These systems are becoming increasingly available throughout Africa.

According to the 2012 UNAIDS report, the use of ARVs in Sub-Saharan Africa has substantially reduced death rates among HIV-positive people. Between 2005 and 2011, the number of people dying from AIDS-related causes in the region declined from 1.8 million to 1.2 million.

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Implications if WHO Guidelines Increase CD4 Threshold for Starting ART to 500 07/03/2013

HIV Treatment Bulletin

1 February 2013. Related: Guidelines.

Nathan Geffen, CSSR

World Health Organization (WHO) guidelines are extremely important. Treatment policies in developing countries are guided by WHO and activists in these countries use WHO guidelines in their advocacy work.

Currently, WHO guidelines recommend that people with HIV start antiretroviral treatment (ART) when their CD4 counts fall below 350 CD4 cells/mm3.

However, several countries have changed their ART guidelines to recommend treatment irrespective of CD4 count or at treatment thresholds of 500 CD4 cells/mm3. [1, 2, 3]

This article looks at the implictions if WHO also recommend that treatment start at 500 cells/mm3 which is one of the changes under consideration.

To understand the impact of the WHO guidelines, consider that there are more people living with HIV in Nigeria than in the whole of North America, Western Europe and Australia combined. Even a small country like Zimbabwe has more people living with HIV than the whole of Western Europe. [4] Sub-Saharan African, Caribbean and Asian countries are strongly influenced by the WHO guidelines, much more so than the Department of Health and Human Services (DHHS) Guidelines published in the United States. This is especially the case for countries where treatment is primarily provided through funding from the Global Fund to Fight AIDS, TB and Malaria (GFATM) or the US President’s Emergency Plan For AIDS Relief (PEPFAR).

The evidence

When considering changing the CD4 initiation threshold, or dispensing with a threshold entirely, we need to consider the evidence of such a change for both an individual patient’s health and for HIV prevention.

Prevention

The HPTN 052 trial showed that ART greatly reduces the risk of an HIV-positive person transmitting HIV to his or her partner. This finding was consistent with compelling observational data. [5]

The WHO subsequently published guidance on couples HIV testing and counselling and this included the recommendation to use antiretroviral therapy for treatment and prevention in serodiscordant couples. [6] Although completed and printed for distribution at the IAS meeing in 2011, this version was withdrawn and publication was subsequently delayed by until April 2012.

There is also evidence from several places including San Francisco, Vancouver and Taiwan that reducing community viral load reduces HIV incidence. [7, 8, 9] There is also evidence from mathematical models that ART is reducing HIV incidence in South Africa. [10]

Nevertheless, for many places it is not unequivocally clear that changing the CD4 initiation threshold to 500 CD4 cell/mm3 would have a significant effect on HIV incidence. In contrast to where reduction in community viral load has been shown to reduce incidence, sub-Saharan African cities have primarily heterosexual epidemics that are possibly in many cases saturated. On balance it is likely that further reducing viral load will reduce incidence in sub-Saharan Africa, but this is not a given. Moreover it has to be discussed with and proven to policy makers too because there are enormous cost implications of beginning this type of expanded treatment. This is why there are studies underway in African countries that will look at whether initiating treatment earlier reduces community incidence. [11]

Treatment

The benefit to the patient should be the salient consideration in the WHO treatment guidelines (as opposed to the couples guidelines in which prevention of infection of the HIV-negative partner is the salient consideration). Caroline Sabin and others have shown that the observational evidence for changing the threshold from 350 is poor and does not meet the increasingly widely adopted GRADE standard. [12] GRADE is a methodology for assessing the quality of evidence. There are four ratings for quality of evidence in GRADE: high, moderate, low and very low. Using the GRADE methodology, the evidence for benefit to a patient from initiating treatment above 350 CD4 cells/mm3 is low.

Moreover, guidelines in some wealthy countries have changed to and fro on the issue of when to start over the last decade and a half: from ‘hit hard, hit early’ to postponing down to much lower thresholds, then to 350 CD4 cells/mm3. This is precisely why the INSIGHT Strategic Timing of Anti Retroviral Therapy (START) [13] and ANRS Early Antiretroviral Treatment and/or Early Isoniazid Prophylaxis Against Tuberculosis in HIV-infected Adults (TEMPRANO) [14] trials are being conducted–to answer once and for all when the best point to start ART is for patients.

One widely circulated myth that needs to be exploded is that HPTN 052 showed that starting above 350 CD4 cells/mm3 reduced disease progression. But the HPTN 052 initiation threshold was 250 CD4 cells/mm3, not 350. Data from clinical trials had previously shown that a treatment threshold of 250 cells/mm3 is inferior. [15, 16] But the question of whether a 350 cells/mm3 threshold is optimal remains unanswered.

There are three likely outcomes of the START and TEMPRANO studies:

  • Earlier treatment is better because it reduces disease progression: the clinical benefits outweigh the risks.
  • There is no difference between the earlier vs. later treatment arms.
  • Earlier treatment is worse because increased side-effects, drug resistance or reduced adherence outweigh the clinical benefit of treatment.

Clinicians and AIDS activists have different expectations of what the trial result will be. But our personal prejudices don’t matter. The evidence is simply not available yet to form an opinion. The WHO needs to wait. [17]

If outcomes two or three turn out to be the case and the WHO has recommended earlier treatment it will undermine the organization’s treatment guidelines. At best there would have been serious cost implications for developing country health budgets; at worst patients might have been harmed. If the WHO keeps its threshold recommendation unchanged, and outcome one turns out to be the case, then the organisation would have simply taken the correct action by having waited for the evidence and in accordance with the principle of first do no harm.

The issue of cost

Cost is profoundly important when considering public health interventions. Activists should always be concerned about cost issues. To ignore them is poor activism, not only because policy makers do not take activists seriously who ignore cost, but because it is morally problematic to ignore cost. Public health policy involves making choices determined by cost. As ART becomes more nuanced, the relative cost per disability life-year saved becomes higher and the arguments for using the money elsewhere become harder to refute. As an example of how cost has informed activism in a developing country, the Treatment Action Campaign (TAC) has been cognisant of cost in its campaigns, despite demanding that the South African government implement treatment and prevention programmes. In a court case that dealt with prevention of mother-to-child transmission in 2002, the TAC included an affidavit that showed the court that the intervention would be cost-saving. Later the TAC published research showing that ART would be affordable for the South African government. By considering cost, the TAC was able to make compelling arguments for the implementation of life-saving interventions.

The current WHO ART guidelines for adults and adolescents included two important changes. [18]

It provided for treatment to be initiated at 350 CD4 cells/mm3 and for stavudine (d4T) to be replaced by tenofovir. Both of these changes have profound cost implications, but they are both supported by a very strong evidence base. Because the campaigns for these changes to be adopted by poor countries have been based on sound science, they have had some success. WHO guidelines should be seen as an achievable aspiration for poorer countries. Nevertheless, even today, several sub-Saharan countries initiate ART at 200 or 250 CD4 cells/mm3 with stavudine. This shows that cost is a critical factor, perhaps the most critical factor, in getting poorer countries to change their guidelines.

Changing the CD4 initiation point from 350 CD4 cells/mm3 in the new WHO guidelines would in our view be premature. It would have profound cost implications on Global Fund, PEPFAR and developing country health budgets. We would be willing to campaign for such a change in guidelines in spite of cost implications if it was supported by evidence. But the evidence is still outstanding. Expecting countries to move to a new CD4 threshold or to dispense with CD4 thresholds without sufficient evidence is a mistake.

One argument that has been made is that some ART sites cannot afford to perform CD4 counts and therefore eliminating CD4 counts from treatment guidelines makes sense. This argument is easily refuted. First, it is much more likely that such impoverished sites will in fact simply ignore guidelines and continue to initiate treatment only when patients are symptomatic. Second there are many sites in sub-Saharan Africa that do CD4 testing that should not have to change their guidelines because there are other places that do not have CD4 counts; guidelines should not be set on the basis of worst practice. Third, sites without CD4 tests almost always initiate with stavudine and it is probably harmful to initiate HIV treatment in people with high CD4 counts on stavudine.

If the WHO recommends a change that is unsupported by sufficient evidence and that has profound cost implications, it risks changing its guidelines from effective advocacy documents that developing countries can realistically aspire to into something that is unrealistic and ignored. This would be unfortunate and possibly harmful to many individuals.

References:

  1. US Department of Health and Human Services’ Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescent.
    http://aidsinfo.nih.gov/contentfiles/lvguidelines/AA_Recommendations.pdf
  2. Several European countries and Australia have a CD4 count threshold of 500 CD4 cells/mm3. See HIV experts on the decision to use early ART for prevention in France: are we there yet?
    http://www.retrovirology.com/content/9/S1/P95
  3. Initiating Antiretroviral Therapy in Treatment-Naive Patients.
    http://arv.ashm.org.au/arv-guidelines/initiating-antiretroviral-therapy-in-treatment-naive-patients
  4. UNAIDS. 2012 UNAIDS Report on the Global AIDS Epidemic.
    http://www.unaids.org/en/resources/publications/2012/name, 76121, en.asp
  5. Cohen MS. et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 August 11; 365 (6) : 493-505. doi: 10.1056/NEJMoa1105243.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200068/
  6. WHO. Guidance on couples HIV testing and counselling – including antiretroviral therapy for treatment and prevention in serodiscordant couples. April 2012.
    http://www.who.int/hiv/pub/guidelines/9789241501972/en/index.html
  7. Das M et al. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PLoS One 2010;5 (6) :e11068.
    http://www.ncbi.nlm.nih.gov/pubmed/15295691
  8. Fang CT et al. Decreased HIV transmission after a policy of providing free access to highly active antiretroviral therapy in Taiwan. J Infect Dis 2004;190 (5) :879-885.
    http://www.ncbi.nlm.nih.gov/pubmed/15295691
  9. Montaner JS et al. Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study. Lancet 2010;376:532-539.
    http://www.ncbi.nlm.nih.gov/pubmed/20638713
  10. Eaton JW. 2012. HIV Treatment as Prevention: Systematic Comparison of Mathematical Models of the Potential Impact of Antiretroviral Therapy on HIV Incidence in South Africa. PLoS Med 9 (7) : e1001245. doi:10.1371/journal.pmed.1001245.
    http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001245
  11. For example, HPTN071 (also known as PopART) is a randomised cluster controlled trial that will be examining the effect of early antiretroviral treatment on community incidence in South Africa and Zambia.
    http://www.hptn.org/network_information/HPTN_newsletter_6.html
  12. GRADE stands for Grading of Recommendations Assessment, Development and Evaluation.
    http://www.gradeworkinggroup.org/.
  13. Strategic Timing of Anti Retroviral Therapy (START).
    http://clinicaltrials.gov/ct2/show/NCT00867048
  14. Early Antiretroviral Treatment and/or Early Isoniazid Prophylaxis Against Tuberculosis in HIV-infected Adults (ANRS 12136 TEMPRANO) .
    http://clinicaltrials.gov/ct2/show/NCT00495651
  15. Severe P et al. Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N Engl J Med 2010;363 (3) :257-265.
    http://www.nejm.org/doi/full/10.1056/NEJMoa0910370
  16. SMART Study Group. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006;355 (22) :2283-2296.
    http://www.nejm.org/doi/full/10.1056/NEJMoa062360
  17. Incidentally one thing that START nor any other realistic randomized controlled trial can measure in a reasonable period of time for guideline considerations, are the very long-term consequences of immediate versus delayed ART.
  18. WHO ART guidelines for adults and adolescents.
    http://www.who.int/hiv/pub/arv/adult2010/en/index.html

 

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Patent Agreement Improves Treatment Access for Children with HIV 01/03/2013

The Ecumenical Advocacy Alliance (EAA) today welcomes the agreement announced between ViiV Healthcare and the Medicines Patent Pool (MPP) that will permit generic manufacture of the anti-retroviral drug abacavir for use with children. ViiV joins Gilead Sciences as the second major pharmaceutical company to join the MPP.

The agreement means that the MPP can issue licenses to ARV manufacturers anywhere in the world for the supply of affordable generic formulations of the drug in at least 118 countries – which account for 98.7% of children living with HIV needing treatment.

“We applaud the transparency of this agreement, in which the Memorandum of Understanding between ViiV and the Pool has been made public, as well as the broader geographical reach of the licensing and the flexibility granted to the Pool to enable new formulations and combinations containing abacavir,” states David Deakin, HIV Programmes Manager, Tearfund UK, and chair of the EAA’s Access to Treatment working group. “Our hope is that these agreements can still go farther, especially with dolutegravir for adults.”

“This is an important step in the treatment of millions of children living with HIV,” states Msgr. Robert Vitillo, special advisor on HIV and AIDS to Caritas Internationalis, and advisor to the EAA’s working group. “We hope that other companies will advance negotiations with the Medicines Patent Pool and will consider licenses for pediatric medications as a first step.”

Anti-retroviral medicines (ARVs) are essential in managing HIV infection, and many of the first line ARVs developed are no longer covered by patents (which usually are applied for 20 years) and thus can be manufactured generically at a lower cost. However, individuals on treatment can develop resistance to the drugs over time, and, in that case, will need to move to second-, and even third-line drugs which are still protected by patents and often prohibitively expensive in resource-poor settings.

Noting that ViiV is also developing a number of very new ARVs which will likely be particularly important for adults, Astrid Berner-Rodoreda, advisor on HIV and AIDS for Brot für die Welt and member of the EAA working group says, “The current pediatric license is a good model for future licenses. We now urge ViiV and other companies to also negotiate licenses for all of their adult ARVs, particularly their second- and third- line drugs.”

Berner-Rodoreda also notes that, “Whilst this license for pediatric ARVs covers more middle income countries, some important countries in Latin America and Eastern Europe are missing which would be crucial to add for future adult ARV licences, as it is estimated that by 2020 83% of people living with HIV will live in middle income countries”.

The MPP was created in 2010 to increase access in low- and middle-income countries to quality, safe, effective, more appropriate and affordable medicines, focusing on HIV and AIDS. The MPP negotiates with patent holders to share their HIV medicine patents with the Pool, and then licenses generic manufacturers to facilitate the production of affordable generic medicines well-adapted for use in resource-poor settings.

ViiV Healthcare is a joint venture between GlaxoSmithKline, Pfizer and Shionogi specializing in HIV-related medicines.

For more information contact:
Sara Speicher

sspeicher at e-alliance.ch

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When Wild Garlic Makes You Pregnant 06/02/2013

God, AIDS, Africa and HOPE

 

Pius Fasinu(left), Prof Bernd Rosenkranz (right) and those involved in the research

 

Pius Fasinu(left), Prof Bernd Rosenkranz (right) and those involved in the research

HOPE Cape Town is not only working on grass root level but also involved in academic research; a holistic view of HIV and AIDS has been at the core of the work of  HOPE Cape Town since the beginning. With the permission of the author we publish this article explaining an exciting research on muti – the medicine of sangomas in South Africa through the PhD student Pius Fasinu:

When wild garlic makes you pregnant

Pius Fasinu

People who use traditional remedies together with conventional medicines may want to rethink their strategy, because the combination of these substances might be doing them more harm than good.

Researchers have found that certain African medicinal herbs, including wild garlic and the African potato, could interfere with how conventional drugs work in the body. The herbs included in the study are traditionally used to treat diseases such as fever, pain, diarrhea, asthma, cold, cough, infections, hypertension, depression and ailments related to HIV and Aids.

Preliminary results of the study being conducted by the Division of Pharmacology at Stellenbosch University (SU) have shown that the herbs can quicken or delay the elimination of conventional drugs from the body. “This adds to the risk of treatment failure or toxicity,” says Pius Fasinu, a doctoral student in pharmacology.

“Patients should tell their doctors if they are taking any herbal medicine, or at best avoid taking the herbs and conventional medicines together,” is Fasinu’s advice based on the findings.

Traditional medicine and especially the use of medicinal herbs are popular in South Africa. “While the use of medicinal herbs predates the emergence of HIV and Aids, a number of indigenous herbs are widely consumed as immune boosters and to manage the symptoms of this disease,” explains Fasinu, who is completing his research under supervision of Prof. Bernd Rosenkranz and Prof. Patrick Bouic of the SU Division of Pharmacology in the Faculty of Medicine and Health Sciences.

The high disease burden and the strong attachment of traditional medical practices to culture and tradition have prompted various African governments to start integrating traditional medicine into the mainstream healthcare.

”Nearly two in every three people who live with HIV and Aids combine their antiretroviral drugs with medicinal herbal products,” adds the doctoral student who is doing an in vitro assessment of selected traditional medications used in South Africa and their pharmacokinetic drug interaction potential.

For purposes of his study, Fasinu consulted traditional healers and used available literature to identify and source the most popular herbal remedies used by people who also rely on conventional healthcare.

African potato (Hypoxis hemerocallidea), fat hen (Chenopodium album), devil’s thorn (Emex australis), cancer bush (Sutherlandia frutescens), sweet thorn (Acacia karroo) and wild garlic (Tulbaghia violacea) were included in the study, and were shown to interfere with the functioning of conventional drugs in the body.

The herbs were not tested for their therapeutic benefit or for their potential toxicity when they are taken on their own. Rather, herb extracts were tested to see what their effect was on the enzymes in the body that are responsible for metabolising and eliminating conventional drugs.

Fasinu’s tests showed that the herbal extracts inhibited the majority of these enzymes. “This suggests that conventional drugs taken with some traditional herbs may accumulate in the body because of the enzyme inhibition,” Fasinu believes. “This leads to toxicity.”

In some cases, herbal derivatives also had the opposite effect, in that it induced the production of more enzymes and therefore sped up the metabolism of the drugs. This could lead to the failure of conventional drug treatment because it is cleared from the body far too quickly to be beneficial. Samples from human livers that contain the active enzymes were used to assess the impact of herbal extracts on drug clearance. It provided the closest scenario to herb-drug combination in humans.

“Hypertension may persist if herbs are taken together with anti-hypertensive drugs, and pregnancy may occur when they are taken with contraceptive pills,” he cites some of the inadvertent consequences of using traditional and conventional treatments together.

“Despite the popularity among South Africans to use herbs and conventional medicine side by side, there is little information available on how safe this practice is,” a concerned Fasinu says. “Considering the potential consequences, it is best to exercise caution.”

 ”Pius Fasinu, with the support of HOPE Cape Town”, phasynou@gmail.com

 

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Early HIV Therapy Boosts Immune Response 04/02/2013

MONASH U. (AUS) — Given within four months of infection, HIV antiretroviral therapy helps the immune system restore T-cells to healthy levels. "In the four months after HIV infection the immune system mounts an immune response and starts to recover naturally before it subsequently progressively declines. This observation tells us that there may be a narrow restorative window that could be targeted for recovery through earlier initiation of potent antiretroviral therapy," explains researcher Edwina Wright.

Patients demonstrated stronger and faster recovery of the body’s CD4+ T-cells than patients who started therapy later. CD4+ T-cells are specialized immune cells required to fight infections and are depleted during HIV infection.

The new insight into the optimal timing of therapy for HIV infection could give patients a better chance of responding to potential cure strategies of the future.

Published in the New England Journal of Medicine, the study drew data of 468 patients followed over a 48-month period in the San Diego Primary Infection Cohort.

The study also found patients with higher counts of CD4+ T-cells at the initiation of therapy demonstrated a stronger recovery of CD4+ T-cell counts than patients who start therapy later.

Wright says further clinical studies were needed to determine whether starting antiretroviral therapy earlier could enhance the chance of patients responding to future cure strategies.

“In the four months after HIV infection the immune system mounts an immune response and starts to recover naturally before it subsequently progressively declines. This observation tells us that there may be a narrow restorative window that could be targeted for recovery through earlier initiation of potent antiretroviral therapy,” says Edwina Wright, associate professor at Monash University.

“Through early therapy, full recovery of the CD4+ T-cell count could make a critical difference to the immune system’s overall health and the individuals capacity to directly fight off infections, tumors, and disease. This knowledge may also better position them to be successful if any HIV curatives come along.”

Wright explains even a short deferral of antiretroviral therapy outside of the four-month window could compromise CD4+ T-cell recovery, irrespective of the CD4+ count at the time of treatment initiation.

Wright and colleagues at Monash University are also involved in a major new clinical trial, the START study, designed to look at the benefits of immediate versus deferred antiretroviral treatment in people with HIV infection.

The trial is being conducted in 30 countries and will recruit 4000 HIV-infected men and women. Participants will be followed for up to five years.

Source: Monash University

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Multiple Factors Affect HIV Prognosis, Study Shows 06/02/2013

In a major advancement for the field of HIV treatment, a new study has identified a more accurate method of suggesting prognosis for HIV patients.

The new method, called the Veterans Aging Cohort Study index, takes into account factors such as hemoglobin level, platelet count and comorbidity. Previous models of predicting HIV-related outcomes depended only on levels of CD4, a glycoprotein found on the surface of immune system T-cells, and viral load, an estimate of the amount of virus present in the body. But as improved antiretroviral therapy has lengthened the life expectancy of HIV patients, these two factors are no longer sufficient in developing a patient’s prognosis, said Amy Justice, a professor at the Yale School of Medicine and chief of general internal medicine for the VA Connecticut Healthcare System.

Two papers on the accuracy of the VACS index, one using data from a North American cohort and the other using data from a European cohort, were published in the journals JAIDS and AIDS, respectively, on Feb. 1.

The VACS index weighs different variables based on their association with mortality, Justice said, adding that prior to this development “doctors didn’t have a good way of combining all the available information together” to make an accurate prediction of life expectancy. Once the index was formulated, Justice and her co-authors evaluated its accuracy by analyzing data from 40,000 HIV patients in North American and European cohorts of the VACS, she said.

The researchers found that the VACS index was more accurate than the restricted indices in predicting HIV-related mortality, Justice said.

“Now that people with HIV are living full lives, we need a way to intervene with complications earlier and we need to get doctors to pay attention to more than CD4s and viral loads,” said University of Toronto professor Sean Rourke, another co-author of the study.

But the implications of these findings go even further than giving individual patients more accurate prognoses.

The new HIV markers identified can be used in clinical trials to test the success of different treatments and to “prioritize medications in terms of their overall benefit and lack of harm,” Justice said, adding that the index may lead to the development of more effective HIV treatments. Her next goal is to continue analysis of similar patient records and, by next year, publish a paper on how risk of mortality changes over time as a patient’s levels of markers such as hemoglobin and platelet count are modified, she said.

Work on the new index began when Justice became interested in the idea of comorbidity and its relationship to HIV outcomes approximately 10 years ago. Justice said she noticed that half of the HIV patients with whom she dealt in the tests she was running were coinfected with hepatitis C, but her idea was initially met with skepticism.

“At the beginning, people thought, ‘Why would we want to look at comorbidity?’ because all they really wanted to do was manage CD4 and viral load,” Justice said. “But the national scene changed once doctors recognized that HIV patients are living longer now, and that there have to be other things going on that we should take into account in our management.”

She added that in many instances a patient’s CD4 and viral load might be at healthy levels, but comorbid factors like liver or kidney failure could still decrease life expectancy.

Rourke said his next goal is to continue studying the link between HIV and neurocognitive impairment, which is a comorbidity that has not yet found its way into scientific literature.

The VACS Index Risk Calculator became available as a website and smartphone app in January.

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Treatment News 2012

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Clubbing Together for Treatment. 30/11/2012

Health-e News
30.11.2012 Anso Thom

  

Antiretroviral therapy (ART) adherence clubs, already operating in several high burden areas in Cape Town, have the potential to revolutionise the treatment of millions of HIV-positive South Africans and lighten the load on overburdened health workers.

Medecins Sans Frontieres (MSF), known for its ability to find novel solutions to pressing health systems problems, this week launched an ART adherence club toolkit that can be rolled out to most public sector clinics, hospitals and communities where almost two million South Africans are being treated.

In a nutshell, the ART adherence clubs are a long-term retention model of care for stable patients on ARVs. Between 20 and 30 patients meet and are facilitated by a non-clinical staff member (often a Treatment Action Campaign counselor) who provides a quick clinical assessment, a referral where necessary and peer support in the form of a short group meeting. Pre-packed ARVs are distributed, enough to last for two months until the next meeting. MSF is keen to extend it to three months.

Once a year, the patient is referred for blood tests and is seen by a doctor.

This means that for one year the patient does not need to be seen by a professional health worker, essentially freeing them up to treat more complex cases and creating space in waiting rooms.

“The critical question we faced was how we place a further two million people in need of drugs on treatment and how we retain the two million already receiving ARVs,” explained Lynne Wilkinson, head of the MSF’s Khayelitsha programme and project co-ordinator for the adherence clubs. Wilkinson was also one of the key partners who managed to successfully establish a similar programme in the deep rural Eastern Cape a few years ago.

Wilkinson believes that if they continued with business as usual, with an increasing number of patients relying solely on healthcare facilities, there is a very real danger that many patients will be at risk of failing their treatment.

“There is no need to waste our scarce resources on patients who are doing well or forcing patients to make different decisions (when faced with spending a day in a clinic waiting for their pills or paying lots of money to travel far),” said Wilkinson.

A pilot study conducted by MSF with the support of project partners - the Western Cape health department, the Institute for Health Improvement and the Treatment Action Campaign (TAC) - showed that after almost four years 97 percent of club patients remained in care.

Club members were also 67 percent less likely to have virological rebound, a marker that indicates good adherence to treatment.

Almost 20 percent of the more than 23 000 patients receiving treatment from nine facilities in Khayelitsha, access it via clubs.

“This programme can be scaled up quickly,” said a confident Wilkinson, who would like to see it rolled out throughout South Africa and sub-Saharan Africa.

The next step for MSF has been to start evening clubs for those patients working during the day – they are able to attend after 6pm. Caregiver and child clubs will allow children requiring treatment to attend with their parents or caregivers. Youth clubs are also being tried for those adolescents in the pre-ART stage or newly initiated onto treatment.

A novel development has been the hosting of the adherence clubs in people’s homes and community venues.

Not surprising, the model has caught the eye of the Western Cape health department which has become a partner in rolling it out to several high burden urban centres in Cape Town and soon to more rural areas.

Dr Jannie Mouton of the provincial health department is unequivocal that “it is the way to go – we need to roll it out into communities and people’s homes”.

Mouton said the province was also looking at integrating the clubs into a chronic care model, which means that patients with for example diabetes or high blood pressure could benefit.

By August this year 149 new clubs had been established in Khayelitsha at nine health facilities. In total 5 195 patients had been enrolled.

Wilkinson says that fixed drug combination (one pill as opposed to three) drugs would allow for the clubs to be expanded even further. This could see the counselor collecting the drugs from a central point and carrying it to the meeting venue in a backpack as opposed to having to drive.

A slightly tweaked model is also being tried in KwaZulu-Natal where community members meet at a health facility for a couple of months. Once patients are able to establish which members live in the same village, they are able to establish clubs close to home. It is envisaged that this version could work in rural areas.

Other than the needs for fixed dose combination drugs, Wilkinson identified the lightening of the load on pharmacists as a critical priority that had to be addressed.

In the Western Cape they were hoping to sidestep this challenge by making use of the Central Dispensing Unit which is able to courier drugs.

The initiative has already won a 2012 platinum award from the Impumelelo Social Innovations Centre and is a finalist in the United Nations Public Service Awards, a prestigious international recognition of excellence in public service.

The Adherence Club model, which won an Impumulelo social innovation award earlier this year(http://www.ihi.org/about/news/Documents/IHIPressRelease_SouthAfricaImpumeleloAward_Sept12.pdf)), is also up for a UN award.

For more information about the toolkit, click here: http://www.msf.org.za/publication/art-club-toolkit

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More Important to get Patients on Sustainable, Affordable Drugs. 26/11/2012

CAPE TOWN - After 30 years of HIV disease it is more important to deal with the costs of the medicines and how to sustain access to it, rather than treatment outcomes, according to an HIV specialist.

26.11.2012
Anso Thom

 

 Addressing the first Southern African HIV Clinicians Society conference today, Professor Brian Guzzard, an expert advisor to the UK government on HIV and head of one of Europe’s largest clinical units, started his talk recalling his visit to South Africa shortly after the release of Nelson Mandela. “The then government told me that HIV will never be a problem in South Africa,” Guzzard told the packed auditorium.

Guzzard said that for the past 10 years they have been trying to get people onto treatment earlier, but that there were no proper randomized trials showing that it should be a priority.

He revealed one study, which was currently taking place, and investigating placing people with HIV on antiretroviral treatment at a CD4 count (measure of the body’s immunity) above 500, was not expected to show any dramatic improvement in outcomes.

He added that studies from the United States showed that patients likely to get onto treatment earlier, as those who are wealthy and often less likely to have a high incidence of HIV infection.

“Thinking of cost and using the appropriate drug is more important that discussing when antiretroviral therapy should be initiated,” said Guzzard.

“We are going to be saddled with treatment for the next 40 years, so let us make it work and accessible. Doctors here need to discuss how to give to the cheapest and simplest treatment to the largest number of patients,” he said.

Speaking in the plenary after Guzzard, Professor Tom Harrison of St Georges University of London focused on cryptococcal meningitis “an every day experience for those working in state hospitals”.

He revealed that 15 percent of all HIV-related deaths were due to cryptococcal meningitis and that current treatment options were inferior. The gold standard treatment is not available or feasible for Africa, according to Harrison.

He added that antiretroviral therapy had not led to any decrease in the incidence of cryptococcal meningitis, but had improved the long-term prognosis for those patients on ARVs.

Harrison said there were enough tools – diagnostics and drugs – available to optimize the management of symptomatic cases.

Cryptococcal meningitis is a fungal infection of the tissues covering the brain and spinal cord (meninges). It is caused by the fungus Cryptococcus neoformans found in soil around the world.

Cryptococcal meningitis most often affects people with a weakened immune system.

The conference continues until Wednesday.

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Nurses as Effective as Doctors in Treating HIV Patients. 15/8/2012

SA government policy gets support from researchers at UCT and University of East Anglia, who identify nurses as preferred health providers for ART programmes.

Health-e News

Nurse-centred care of HIV patients can be just as safe and effective as care delivered by doctors and has a number of specific health benefits, according to a new study led by the University of Cape Town (UCT) and University of East Anglia (UEA).

Published on 15 August 2012 in The Lancet, the research shows that neither survival rates nor virus suppression reduced when nurses prescribed antiretroviral therapy (ART) drugs to patients in South Africa. Health benefits included: significantly improved detection of tuberculosis, increased white blood cell count and weight, and adherence with the treatment programme.

It is a priority of the World Health Organisation to expand access to ART, but in South Africa access to the right drugs is limited by a chronic shortage of trained doctors. The government is trying to shift healthcare provision from doctors to primary care nurses, who are more plentiful. This policy has been resisted by some HIV physicians and nurses, however, who feel administration of these drugs is the proper domain of doctors.

More than 15,000 patients took part in the two-year randomised controlled trial in the Free State. All 31 clinics providing ART in the province at the time of the study took part. The study was conducted by UCT in partnership with UEA and other universities.

South Africa has around 6 million people infected with HIV – more than any other country in the world. Of those patients who would benefit from ART less than one in three receive it. In the West, this figure is nearer to 100 percent.
Joint lead author Dr Lara Fairall of UCT said: “The findings profile nurses not just as an alternative when no doctors are available, but as the preferred health provider for ART programmes, delivering better quality care and health outcomes for patients. But we caution against viewing task-shifting as a panacea for the ART access problem. This trial showed no impact on ART access, in part because it was a pragmatic trial designed to test out task-shifting under real-world conditions, which included disruption of control conditions and a three-month moratorium on ART initiations.”

Professor Max Bachmann, of Norwich Medical School at UEA, said: “There is a critical need to improve access to antiretroviral drugs – not only in South Africa but in other low- to middle-income countries where infection rates are high and doctors are in short supply. HIV programmes worldwide should now consider expanding nurse-centred care, safe in the knowledge that there need not be detrimental effects on patient health or mortality rates if done carefully.”

The study is the first to explore “task-shifting” from doctors to nurses on such a large scale. It ran from 2008 to 2010 and was funded by the UK Medical Research Council, Development Co-operation Ireland, and the Canadian International Development Agency. The project was limited to South Africa, but the findings could have relevance in the West where antiretroviral treatment is usually provided by specialist hospital doctors.

Dr Fairall, Professor Bachmann and colleagues are currently undertaking further research to explore the cost-effectiveness of task-shifting HIV care from doctors to nurses, as well as strengthening the primary care of other chronic diseases. 
 

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Dramatic Increases in Life Expectancy in a High-burden HIV Setting Due to ARV Rollout. 25/7/12

The survival benefits in economic terms were also found to far exceed the cost of ARV treatment

AIDSMap

By Lesley Odendal
25 July 2012

The first evidence of dramatic changes in adult life expectancy in an HIV-endemic region, from individually measured data in a complete population cohort, showed large increases in adult life expectancy since the roll-out of antiretroviral (ARV) treatment. The survival benefits in economic terms were also found to far exceed the cost of ARV treatment, according to a study of the effects of ARV in rural Kwazulu-Natal, South Africa, presented by Jacob Bor at the 19th International AIDS Conference (AIDS 2012) in Washington DC.

A complete population cohort of 149,640 individuals in a community in rural KwaZulu-Natal, with an adult HIV prevalence of 28%, was followed longitudinally between 2000 and 2011. Continuous time data on dates of birth and death were collected through semi-household surveys where the response rate was greater than 99%.

Between 2000 and 2003, the life expectancy of this population fell from 59 years to 52 years due to high rates of HIV infection and lack of access to ARV treatment. However, since 2003 – when ARVs became available through the public health system – there has been a gain of 8.2 years in life expectancy from 52.4 years in 2003 to 60.6 years in 2011. The adult life-expectancy years gained were found to be 9.5 years for women, compared to 6.6 years for men. Regardless of exposure to HIV, there has been a 13.9 year increase in median life expectancy of a typical person.

Researchers calculated that the cumulative estimated monetary value of life-expectancy gains to a 15 year old was US$79,000. This compared to the present discounted value of an individual’s lifetime contribution to the community’s expected treatment costs for ARVs, which was found to be US$2400. This model assumes that HIV treatment would cost US$500 per patient, per year.

“When we compare the economic gains of keeping people alive through ARVs and how this assists them in contributing to the economy with the relatively small cost of ARV treatment, it only makes economic sense to keep providing ARV treatment to as many people are need it. Beyond the moral arguments for keeping people alive, groups who think in monetary terms only can see from our data that keeping people on treatment is economically beneficial,” said Mr Bor.

Although changes in population life expectancy have been modelled, they have not yet been measured using actual data. For the first time, this study measured changes in population-level adult life expectancy associated with the rollout of ARV treatment, in a setting of very high HIV prevalence. Researchers hoped that by using population-level outcomes that capture the spillover effects of the availability of ARVs, this would allow individuals, donors and governments to see the value of ARV programmes when making decisions regarding ARV investments.

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AIDS Breakthrough as Study Says Treatment should Cost Less. 20/7/12

Clinton Foundation delivers report showing cost of treating people with HIV is four times less than previously thought

15 July 2012

Lack of money can no longer be considered a reason – or an excuse – for failing to treat all those with HIV who need drugs to stay alive, following game-changing work about to be published by the Clinton Foundation that shows the real cost is four times less than previously thought.

The striking findings of a substantial study carried out in five countries of sub-Saharan Africa are hugely important and will set a new hopeful tone for the International Aids Conference in Washington, which opens on Sunday. It will help make the argument for Barack Obama and other international donors to dig deeper into their pockets – because the cost of saving lives, slowing the spread of HIV and achieving the ambition of an Aids-free world is lower than anyone assumed.

The work by the Clinton Health Access Initiative (CHAI) shows that the total cost of treatment in health facilities – including drugs, lab tests, health workers' salaries and other overheads – comes to an average of $200 a patient a year across Ethiopia, Malawi, Rwanda and Zambia – four of the Aids-hit African nations studied. That rises to $682 in South Africa, which has higher salaries and lab costs.

Until now the generally accepted total cost of treating a patient for a year was an average of $880 – based on a study by the US president's emergency plan for Aids relief (Pepfar) released at the last International Aids Conference two years ago in Vienna.

Bernhard Schwartländer, director of strategy at UNAids, believes the CHAI work should lead to new optimism. "I think the cost argument is just a false argument and it has been used as an escape. We do need more money but it is not at a level that will be impossible," he said.

The costings are particularly important in the wake of recent scientific findings that show putting people on antiretroviral drugs makes them far less likely to infect others – helping to stop the spread of HIV as well as keeping people alive. CHAI will also announce that it has negotiated down the prices of some of the newer and most important drugs needed for treatment by around a third.

Former US president Bill Clinton hailed the findings as evidence that all 15 million people with HIV in need of treatment could affordably get it – the target for 2015. At the moment, 8 million are being treated. "We now have compelling evidence that universal access to high-quality HIV treatment is achievable, sustainable, and within our means," said Clinton.

"Together, the costing study and price reductions open the door to scaling up and sustaining services for the 7 million people who currently lack access to HIV treatment. Providing treatment will save lives and help prevent the spread of HIV."

CHAI worked with the Centre for Global Development and the governments of those African countries involved to collect data from 161 health facilities for the last financial year on record – mostly 2010.

The original aim of the study was to find out whether there was any potential to reduce waste, cut costs and save money, but researchers found salaries and other costs were already so low that this was unlikely, except possibly in South Africa.

Average costs per patient were lowest in Malawi, at $136 a year. That rose to $186 in Ethiopia, $232 in Rwanda and $278 in Zambia. Nearly half the cost, on average, was the price of drugs – which will increase slightly as countries begin to use more effective and more expensive drugs now recommended by the World Health Organisation. CHAI, however, is about to announce a deal with generic drug companies, which will reduce tenofovir-based regimens, which are the "gold-standard" in the USA and recommended by the World Health Organisation, to $125 from $339 in 2007. CHAI says this will save countries over $500 million between now and 2015.

Kate Condliffe, executive vice-president for HIV programmes at CHAI, said finances were thought to be a bottleneck to expanding the numbers of drugs in many countries. "The perception that treatment costs are higher is casting a cloud over conversations on how to accelerate treatments," she said.

"You sit through conversations on treatment and prevention where there should be incredible optimism, given the science, and yet there is concern about feasibility and cost that lead to an incremental approach."

But while there are not huge opportunities to save money on treatment in the clinics, there is a disparity between the costs at health facilities and the costs at government level. That was illustrated this week in the major UNAIDS report, which referred to national costs in Zambia – around a third higher than costs in the clinic.

Schwartländer said that even if one assumed a cost of $300 a patient a year, the bill to put 20 million people on HIV treatment would be $6bn a year. "It is not outrageous. It can really be handled," he said. "Look at the amount of money moving around in low-income countries. $6bn should not shock us – it is not impossible. We need a different view from that of the 'treatment timebomb'."

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Decriminalization of Drugs as HIV Prevention. 11/7/12

What stops HIV? The answer—issued this week by a commission of leading experts assembled by the UN—is an end to the criminalizing of drug use, needles, and personal possession of drugs.

11 July 2012

What stops HIV? The answer—issued this week by a commission of leading experts assembled by the UN—is an end to the criminalizing of drug use, needles, and personal possession of drugs.

Public health experts long ago realized that laws and policing were as important as clean needles, condoms, and antiretroviral treatment to stopping the AIDS epidemic. But the UN and UN-sponsored commissions-never famous for boldness-have stopped short of addressing drug possession laws, talking instead about stigma reduction, harm reduction, and "decriminalization of drug users." That changed yesterday, when UNAIDS head Michel Sidibe, UNDP Administrator (and former New Zealand Prime Minister) Helen Clark, Deputy Secretary General Jan Eliasson, and other notables gathered at the UN to salute the findings of the Commission on HIV and the Law, which included a clear call for reform of laws that make drug possession (rather than dealing) a crime.

The 145-page report by the independent commission, which included former presidents of Botswana and Brazil, senators, supreme court justices, and leading human rights and health experts from six continents, also called for the decriminalization of sex work, same sex relations, and HIV transmission, and urged developed countries to stop pushing poorer nations to buy expensive brand-name medicines. But the boldest call in the book was the recommendation to remove criminal penalties for drug possession. The commissioners highlighted the dangers of failure to reform drug policies, singling out countries like Russia and Thailand whose war-on-drugs approach they said helped facilitate HIV epidemics. The commissioners also urged the United States to remove its prohibition on federal funding for needle and syringe programs.

This is the second expert report to highlight the way bad drug policy accelerates the effects of HIV in as many weeks: the Global Commission on Drug Policy, including still more former presidents and dignitaries, released a report on June 26 documenting how the war on drugs has worsened the AIDS epidemic and calling for decriminalization of drug use.

Expert consensus, including that of politicians who have served at the highest levels of leadership, is now clear. Putting health first means not putting people in prisons simply because they use drugs. Let's hope the drug decriminalization message reaches every UNDP office, presidential palace, White House, and senate hall in the world, and is echoed from the podium at the upcoming International AIDS Conference in Washington. And even more importantly, let's hope real law reform happens. For the thousands languishing in prison who shouldn't be there, and for the communities and countries watching injection driven HIV epidemics grow to include non-drug users, this is one policy change that must not wait.

 

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Patients Warned Not to Stop ARVs after Woman Suffers Enlarged Breasts. 25/6/12

HIV clinicians have urged patients on antiretroviral therapy not to stop taking the life-prolonging drugs.

City Press

By Zinhle Mapumulo
25 June 2012

HIV clinicians have urged patients on antiretroviral therapy not to stop taking the life-prolonging drugs.

This comes after media reports about a woman whose breasts enlarged abnormally after taking ARVs.

Dr Francesca Conradie, president of the Clinicians Society, said: “Lipodystrophy or change in fat distribution in the body is a well-known side effect that is associated with ARVs.”

However, it was not common, she said.

Last week the Sowetan newspaper published a story of a 29-year-old woman whose breasts had overgrown.

She was diagnosed with lipohypertrophy.

She blamed her condition on the ARVs she began taking in 2006.

However, Professor Francois Venter, former president of the Clinicians Society, blamed her condition on the lack of attention by healthcare staff.

“It should never, ever get this severe,” he said.

“This condition presented in the case of people on ARVs. If slight breast enlargement is noticed, the patient should bring it to the attention of a healthcare worker, and the (specific) drug should be stopped,” Venter said.

Dr Sindi van Zyl, a general pracitioner from Johannesburg, agreed.

“Doctors and nurses that are trained in HIV management should know which early signs to look out for.

“When these signs are picked up we try to switch the patient to a better drug,” Van Zyl said.

The ARV drugs that have been found to be linked to lipohypertrophy are efavirenz and stavudine. Stavudine was phased out in April 2010 as one of the drugs prescribed to adults starting with treatment.

However, efavirenz was introduced at the same time.

Venter said it should be noted that while efavirenz is associated with lipohypertrophy, “it is still a fantastic drug.”

“But, like all drugs, it has some side effects. If you get breast enlargement, simply switching it quickly will do the trick,” he said.

Conradie shared the same sentiments but also warned that certain reasons such as previous resistance or TB infection may mean a patient cannot switch to other drugs.

Both Conradie and Venter advised people on HIV treatment to continue taking ARVs.

“This is a known side effect and this extent is very uncommon,” said Conradie.

While Venter said: “If anything is worrying you, bring it to the attention of the health worker.

“In almost all cases, we should be able to help – if you are dissatisfied, try someone else,” he said

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Truths, Lies and Antiretrovirals. 8/6/12

Although you can never stop taking antiretrovirals, rumours that these little pills will drive you mad are a bald-faced lie, writes Mia Malan.

Mail&Guardian

By Mia Malan
8 June 2012

South Africa today has the largest public-sector HIV treatment programme in the world, in stark contrast with a decade ago, when court cases and protests to force a resistant government to make HIV drugs available were the order of the day.

About 1.5-million of the country’s 5.4-million HIV-infected population now receive about antiretrovirals (ARVs) that slow down the replication of the virus in their bodies.

But over the years many myths about ARVs have arisen.

The Mail & Guardian spoke to Dr Sindisiwe van Zyl of the Johannesburg-based Anova Health Institute’s HIV programme to demystify seven of these fallacies.

Myth 1: Everyone with HIV needs ARVs

Doctors use a CD4 count test – an indication of the strength of a person’s immune system – to determine whether an HIV-infected person needs ARVs. Only when a patient’s CD4 count drops below a certain level do ARVs become necessary. In the state sector, everyone who is HIV positive with a CD4 count of 350 and less is put on ARVs. In the private sector, patients are started on treatment earlier, at a CD4 count of 500.

However, if someone with HIV has tuberculosis (TB) as well, the person is put on ARVs regardless of his or her CD4 count. According to medical website WebMD, healthy HIV-negative people have CD4 counts of between 500 and 1500.

Myth 2: You can stop and start your ARVs

ARVs are a lifelong commitment. If you stop taking them, you are likely to get sicker than before. During the period that you stop taking your medication, you give HIV a chance to become resistant to the ARV drug combination you are taking and that regimen may not work for you again.

Myth 3: Once you have become resistant to your ARVs, there is nothing doctors can do for you

HIV can become resistant to your ARV regimen when you interrupt your treatment or fail to take your drugs at a set time every day. In such cases, it is possible to replace your ARV combination with a new regimen that will still work for you. It will, however, have more side effects and cost more.

When you start taking ARVs, you will generally be put on a regimen of three pills known as first-line treatment. This is the most affordable line of drugs with the fewest side effects. If you become resistant to these, you will be moved to the second line of drugs, which are more expensive and have more side effects. In the case of the second line  drugs becoming ineffective, you will be referred to a tertiary hospital where you will receive a much more complex drug combination referred to as third-line or salvage therapy.

This regimen often consists of four and not three types of ARVs and may not suppress the virus as effectively as the first- and second-line drugs.

Myth 4: ARVS give you a thin face and deform your body

Until recently, the most commonly used ARV regimen at government hospitals included an ARV known as d4T. If d4T is used for longer than a year, it can change a patient’s body shape, causing fat loss in the arms, legs or face or depositing fat in the stomach, back of the neck or breasts (in men and women). In April 2010, d4T was replaced by a drug known as Tenofovir, which has none of these side effects.

Myth 5: ARVs drive you mad

An ARV known as Efavirenz often causes people to have bizarre dreams and makes them feel dizzy and drowsy. Some people have interpreted these side effects as the onset of insanity. These reactions usually disappear within three weeks of starting to take the treatment.

Myth 6: You cannot take ARVs and TB treatment together

Everyone who is infected with HIV and has TB has to take ARVs. If you developed TB before starting your ARV medication, the TB treatment has to be started two weeks ahead of the ARVs. This gives your body the chance to first adjust to the TB drugs.

Patients with undiagnosed TB, who are started on ARVs while they have TB, often develop a condition known as TB-IRIS during which the immune system overreacts to all the medication and the TB becomes worse. It is therefore very important that doctors and nurses screen HIV patients properly for TB.

If you have been on ARVs for a while and the treatment is effective, you are unlikely to develop HIV-related illnesses including TB. But if you do, you can take the TB treatment immediately, as your body has already adjusted to the ARVs.
An ARV known as Nevirapine cannot, however, form part of your antiretroviral drug combination if you’re on TB treatment. Nevirapine interacts with a TB pill known as Rifampicin. Instead, Efavirenz will be included in the ARV regimen.

Myth 7: Babies cannot take ARVs

Babies can take special ARV syrups from as early as two weeks of age. Government guidelines require all babies infected with HIV to be put on ARVs immediately. In the state sector, infants are usually tested for HIV only at six weeks, when their mothers take them to the clinic for vaccinations. In the private healthcare industry, this happens at four weeks. However, if the child falls ill shortly after birth, the baby can get tested for HIV immediately.

Without preventative treatment during pregnancy, a mother has a 40% chance of transmitting HIV to her baby. Prevention-of-mother-to-child transmission of HIV programmes have reduced the risk to 2%.

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When Infection Won't Quit. 4/12

TB, AIDS, and malaria are finding new ways to resist treatment

April 2012

Recent headlines paint an insidious trend in infectious disease. In San Francisco, 60 percent of new HIV infections are drug resistant. In Europe and the U.S., a deadly new form of tuberculosis — dubbed extremely drug resistant, or XXDR-TB — defies nearly all available antibiotics. And in parts of Asia, the newest treatment for malaria has lost its potency, portending a spike in malaria deaths worldwide.

Rising drug resistance has turned what public health officials call today's Big Three infections — HIV/AIDS, tuberculosis, and malaria — even more fearsome. Together, these diseases kill millions every year, representing 10 percent of all deaths globally. Worse, the trio of epidemics is tragically interconnected, with TB, for example, the leading cause of death among individuals infected with HIV.

The price of success

"Drug resistance is the product of success: With treatment, we have drug resistance," explains Eric Rubin, professor of immunology and infectious diseases at HSPH. So far, says Rubin, new drugs have helped doctors stave off the threat. A continuous stream of treatments for HIV has extended patients' lives. More drugs for TB have entered the pharmaceutical pipeline than for any other bacterial infection. And novel anti-malarial compounds will soon enter clinical trials. "I'm optimistic about the ability to innovate. I think it will continue," says Rubin. "But when poverty and poor access to health care occur together, resistance becomes a much bigger problem. Until brand-new drugs are widely available, a lot of people are going to die."

How Resistance Emerges

Since the dawn of the antibiotic age, beginning with penicillin in the early 1940s, microorganisms have invariably figured out ways to defy or elude the newest addition to the medical armamentarium. And while the causes of resistance play out differently in HIV/AIDS (a virus), TB (a bacterium), and malaria (a parasite), the basic story line is the same. 

Drug resistance occurs when infectious agents change in some way that reduces or eliminates the effectiveness of drugs or chemicals designed to cure or prevent infections. Sensitive organisms are killed, while resistant germs are left to grow and multiply. The more we use antimicrobials, the more resistance to these drugs emerges.

At HSPH, several of the world's top researchers on drug resistance are grappling with the issue in today's Big Three epidemics — leading a counter-resistance to one of public health's most urgent problems.

Tuberculosis

Tuberculosis kills more adults worldwide than any other infection, claiming about 2 million lives annually, a figure that includes more than 450,000 people also infected with HIV. Each year also sees 10 million new cases of the infection.

In the public health lexicon, tuberculosis has acquired an alphabet of names denoting treatment failure. First, in the late 1980s, came multidrug-resistant tuberculosis — MDR-TB: resistant to the standard six-month treatment using first-line drugs (isoniazid and rifampicin). MDR-TB can take two years to treat with drugs that are more toxic and 100 times more expensive than first-choice drugs. More than 5 percent of cases worldwide are MDR-TB, with the highest rates (in some cases, more than 20 percent of cases) in countries of the former Soviet Union and China.

In 2006, after drugs to treat MDR-TB were mismanaged, extensively drug-resistant tuberculosis (XDR-TB) emerged. XDR-TB resists all the most effective drugs — that is, first-line antibiotics, plus any fluoroquinolone and any of the second-line anti-TB injectable drugs. It is especially common among drug-resistant cases in the former Soviet Union, where a weakened public health infrastructure meant that TB patients were no longer carefully treated and monitored. A World Health Organization survey published in 2008 found MDR-TB in 72 countries and XDR in 49, including the U.S.

The Problem

A disease of poverty, TB no longer responds to established treatments — which themselves sicken patients.

The Solution

First, new classes of medications that are better tolerated and that work over shorter periods. Just as urgently needed are new tools for rapid and accurate diagnosis of drug-resistant TB — tests that can be easily used by health workers, even in remote settings.

Today, the situation is grimmer — with cases of extremely drug-resistant tuberculosis, XXDR-TB, resistant to all first- and second-line anti-TB drugs. Though researchers have published just a handful of reports on the disease, the highly defiant bacterium may have been lurking for a long time. "For many years in Eastern Europe, they found unbelievable drug resistance — cases resistant to 20 different antibiotics," says Rubin. And because tuberculosis is spread via droplets released in the air with a cough, healthy individuals can contract the fully drug-resistant strains of the infection just by breathing them in.

Though TB acquires its drug-resistant genetic mutations slowly, once such a mutation crops up, it sticks around. "When you hear about MDR-TB and XDR-TB, what you're really hearing about are TB cases that have a whole pile of mutations," says Rubin. "It's not a single mutation that makes them MDR or XDR, but single mutations for every drug to which they're resistant."

Tuberculosis is a disease of poverty. Initially, resistance arose when patients did not or could not take their medications — which carry unpleasant side effects — for the required time. The more resistant the disease, the less effective and more toxic are the drugs used to beat it.

The emergence of MDR and XDR strains also reflects deeply-rooted problems in medical care. In poor locales, doctors can't rapidly diagnose resistant strains of the bacterium, lacking the means to do sputum culturing and drug-susceptibility testing, all timely and expensive procedures that must be performed in competent labs. Without such technical support, physicians treat all patients with standardized drugs, which may lead to failure if the patients happen to carry strains impervious to the medicines. And drug supplies regularly run out.     

"For TB, we have a double whammy," says Rubin. "There's disease out there [XXDR-TB] that we can barely treat right now. And the drug-resistant disease that we can treat requires very expensive therapy. Parts of the world just don't have the resources for treatment."

HIV/AIDS

With HIV/AIDS, the pattern of drug resistance is precisely the opposite of that of TB: Affluent nations have borne the brunt of drug resistance since 1987, shortly after the anti-retroviral AZT was introduced, followed by an expanding array of state-of-the-art medicines. Ten years ago, 1 to 5 percent of HIV patients had drug-resistant strains of the virus. Today, 5 to 30 percent of new HIV/AIDS cases are drug resistant; in the U.S., the estimate is 15 percent. 

In wealthy countries, more than 30 AIDS drugs have been approved, representing five classes that each work in different ways. Indeed, there are now more drugs licensed against HIV than against all other viral diseases combined. With far longer life expectancy, HIV infection is no longer the death sentence it once was.

The Problem

Already a problem in developed nations, rising HIV drug resistance looms in hardest-hit sub-Saharan Africa.

The Solution

DNA-based tests that can detect resistance mutations. Also, treatment with the right drug combinations followed by monitoring.

 

In developing countries, the story is different. They have relied on a narrow selection of older drugs. Yet while these nations should, theoretically, face less drug resistance-because there have been fewer drugs for the virus to resist — scientists haven't actually measured the problem. "It hasn't been studied nearly as much in Africa or Asia, even though the viruses of Africa or Asia, especially HIV-1C, are much more common in the world," says Max Essex, Mary Woodard Lasker Professor of Health Sciences in the Department of Immunology and Infectious Diseases. According to the WHO, 56 percent of all infections globally are HIV-1C. But drugmakers and public health analysts have focused until now on resistance in HIV-1B, the strain that predominates in the U.S. and Europe, where the lucrative treatment market is based.

Because HIV both replicates and mutates rapidly, drug resistance has been a problem since treatments began rolling out. Even with the most effective antiretroviral drugs, some viruses survive — including the mutants that can resist anti-retrovirals. "Late in infection, every HIV-positive individual is actually infected with a gazillion different viruses at once," says Eric Rubin. "Resistance arises very quickly in HIV because of the preexisting population of resistant bugs. And it arises in a single person."

Not complying with a drug regimen fosters resistance. So does taking one drug at a time, as opposed to a combination of drugs that can keep viral levels down. This was true in the U.S. in the late 1980s and early 1990s, when treatments first hit the market, and is proving to be the case today in Africa, where local physicians may not have access to effective three-drug combinations.

In Africa, drug resistance also sprang up when mothers who were about to give birth received a single dose of nevirapine, an anti-HIV drug that reduces transmission of the infection to their offspring. Belatedly, researchers discovered that the medication triggers resistance to a key class of anti-HIV drugs known as NNRTIs, meaning that the mother couldn't be treated with that group of drugs if she needed them later.

In sub-Saharan Africa, where the epidemic is concentrated, the specter of drug resistance looms large. Essex worries about the growing ranks of newly infected patients who have acquired infections resistant to the drugs known as reverse transcriptase inhibitors, such as AZT and tenofovir, which are largely the only drugs currently available.

"It's particularly scary in Africa because the epidemic is so different there, with women representing 60 percent of those infected," Essex says. "If a significant number of women become infected with drug-resistant variants of HIV-let's say it's 10 or 15 or 20 percent-those women will give birth to infants who are infected, because the drug regimens used to prevent transmission won't work. Having infants or children infected is, in one sense, an even greater problem than adults, because you have to treat them for their entire lives." Lifelong treatment with antiretrovirals could also leave patients more vulnerable to chronic conditions in adulthood, such as cardiovascular disease and stroke.

Malaria

Malaria kills someone in the world every 30 seconds. Most of its victims are children living in Africa south of the Sahara. In 2009, the WHO announced that the emergence of parasites resistant to the newest anti-malarial drug — artemisinin — could undermine the success of global malaria control. Initially spotted along the Thailand-Cambodia border, it has since appeared as well in Vietnam and Myanmar.

The news didn't surprise Dyann Wirth, chair of the Department of Immunology and Infectious Diseases and Richard Pearson Strong Professor of Infectious Diseases at HSPH. "For every new anti-malarial that's been introduced, as with any microorganism, resistance has appeared," she says. Along the Thailand-Cambodia border, the appearance of drug resistance may be partly attributable to patients taking too little medicine, substandard medicine, or counterfeit preparations with a tiny amount of the active drug; a 2010 WHO report found similarly poor-quality treatments in Africa. Once established, the drug-resistant strains spread via mosquitoes — the infection's carrier in nature.

The Problem

The malaria parasite has shown signs of resistance to the newest drug to combat the infection.

The Solution

Determine if a patient is infected with a resistant strain and choose the right medications from the outset, instead of waiting for a drug to fail.

 

As Wirth and her colleagues at the Broad Institute have discovered, the genome of the most virulent malaria parasite — Plasmodium falciparum — is highly diverse. That genetic diversity plays a major role in both the emergence and spread of drug resistance. Mutations occur spontaneously. Some happen as a result of natural selection after exposure not only to modern malaria drugs, but also to the traditional medicines used to treat fevers, which may lead to cross-resistance with current drugs. Wirth also found genes that confer resistance to multiple drugs — not unlike the MDR genes in bacteria. "These are probably key players in the modulation of resistance," she says. "They may allow parasites to survive in the presence of drugs, and perhaps permit other mutations to be selected."

As Wirth sees it, the public health impact of drug resistance in malaria depends on how well a resistant organism spreads through human and mosquito populations. Indeed, most of the parasites unfazed by today's drugs appear to have descended from common ancestors, suggesting that they have acquired an ability to survive in the complicated human-mosquito cycle of transmission.  "If drug resistance is going to be a problem beyond an individual, then it has to spread," she notes. "And to spread, it has to compete with all the other parasites out in the world. It has to compete for a place in the mosquito, and it has to compete for a place to get transmitted to the next person."

In this population-level perspective, drug resistance tends to arise over long periods of time in places where humans and mosquitoes share the same terrain. If a drug-resistant mutation crops up and is capable of spreading, the parasite population suddenly shifts from being sensitive to being impervious to a drug.

At the moment, malaria is a treatable disease, Wirth says. "But artemisinin is the last drug we have in the armamentarium. If artemisinin resistance spreads, there will be the same situation as in the 1980s and 1990s. You'll begin to see more serious malaria and more childhood deaths on the African continent."

Compounding the problem is rising pesticide resistance in parasite-bearing mosquitoes. During the Global Malaria Eradication Program of the 1950s and 1960s, early success collapsed when mosquitoes became resistant to the solely used insecticide DDT. As a result, malaria resurged to previous or even higher levels. Today, that threat has returned with wide distribution of insecticide-treated bed nets and accelerated indoor spraying campaigns. Scientists fear that such measures may foster resistance to all four classes of insecticides used today, undermining any progress in human clinical treatment.

— Madeline Drexler is editor of the Review, and author of Emerging Epidemics: The Menace of New Infections (Penguin, 2010).

Tuberculosis image/SPL/Photo Researchers, Inc.
HIV image/Dr. Klaus Boller/Photo Researchers, Inc.
Malaria image/Eye of Science/Photo Researchers, Inc.

 

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Guidelines Developed to Help Boost Rates of Entry into HIV Care, Retention in Care and Levels of Adherence. 20/3/12

Guidelines make 37 specific recommendations and outline priorities for future research.

AIDSMap

By Michael Carter
20 March 2012

New guidelines have been developed to improve the entry of patients into specialist HIV care and assist in their retention in this care. Published in the Annals of Internal Medicine, the guidelines make 37 specific recommendations and outline priorities for future research. The guidelines were developed by an expert panel convened by the International Association of Physicians in AIDS Care (IAPAC) in consultation with physicians in North America and Europe, and are based on the results of clinical studies.

“Entry into and retention in medical care is a prerequisite for providing lifesaving treatments to persons with HIV,” write the authors. “To assure that implementation is feasible for evidence-based recommendations, it will be necessary to strengthen resources, including multidisciplinary linkages dedicated to ART [antiretroviral therapy] and care adherence.”

Improvements in HIV treatment and care mean that the prognosis of many HIV-positive patients is now near normal. However, research conducted in the US suggests that approximately a third of patients are not linked to specialist care within the first year after their diagnosis. Moreover, a significant proportion of  patients who do enter care are subsequently lost to follow-up. Many patients also find it difficult to adhere to their antiretroviral therapy. These factors help explain why only 28% of HIV-positive individuals in the US have an undetectable viral load.

IAPAC therefore convened a special panel to develop guidelines to improve rates of entry into care, retention in care and adherence to therapy. They also made recommendations for the support of specific groups of patients, including pregnant women, incarcerated individuals, children and adolescents, the homeless and those with unstable housing.

The recommendations are based on the results of 325 published studies. These were either randomised controlled trials or observational studies with a comparator group. To be considered by the authors the studies also had to report on at least one biological or behavioural outcome.

A poor evidence base in some areas meant that the investigators also made recommendations outlining future research priorities.

Recommendations: entry and retention into HIV care

-Systematically monitor successful entry into care and retention in care for all patients.

-Case management is recommended for all newly diagnosed patients.

-Intensive outreach should be implemented for individuals not linked to care within six months of their diagnosis.

-Peer support has been shown to improve retention rates for cancer patients and there is some evidence that it improves outcomes among patients with HIV.

Monitoring adherence to antiretroviral therapy

-Self-reported adherence should be routinely monitored in HIV care. To ensure that patient recall is reliable, questioning should focus on adherence over a short time interval (i.e. the previous week).

-Pharmacy refill monitoring is also recommended.

-Routine monitoring of drug levels is not recommended. This is because of the variable levels of concentrations between products and individuals.

-Routine pill counts are not recommended.

-Routine directly observed therapy is not recommended.  However it may be considered in specific circumstances.

-Electronic drug monitoring is not routinely recommended.

Improving adherence

-Once-daily regimens are recommended when regimens have similar efficacy and tolerability.

-Patients taking poorly-tolerated or complex combinations should be switched to once-daily therapy if a potent and safe regimen is available.

-Fixed-dose combinations are recommended when regimens are of equal efficacy and safety.

Adherence tools for patients

-Alarms and text message reminders are recommended, especially if they have an interactive component, for example requiring a reply.

-Adherence counselling that incorporates adherence tools has been shown to be beneficial.

Health system and service delivery interventions

-Nurse- or counsellor-lead adherence support provided in the community  has outcomes similar to those provided by a doctor or in a clinic. This form of support is recommended in resource-limited settings.

-Support and case management should address issues including food insecurity, housing and transport need.

-Support should be provided by an integrated team of professionals, which includes physicians, nurses, dieticians, pharmacists and social workers.

-Directly observed antiretroviral therapy is not routinely recommended. However, it can have benefits for some vulnerable and marginalised populations.

Support for pregnant women

-Targeted treatment for the prevention of mother-to-child transmission improves adherence to HIV therapy for this purpose and is recommended over an untargeted approach.

-Labour ward-based treatment to prevent maternal transmission is recommended for women who are not taking HIV therapy before labour.

Individuals with substance misuse disorders

-Methadone replacement therapy is recommended for individuals with opioid dependence.

-Directly observed antiretroviral therapy is recommended for patients with substance use problems.

-Integration of directly observed HIV therapy and methadone replacement therapy is recommended for individuals with opioid dependence.

Mental health

-Patients should be routinely screened for mental health problems. Counselling and cognitive behavioural therapy can improve adherence in the context of depression and other mental health disorders.

Incarceration

-Directly observed HIV therapy is recommended for patients during incarcerated and following their release.

Homeless patients and individuals in marginal housing

-Patients with no or unstable housing should be provided with case management which focuses on the multiple barriers to adherence which they face.

-All homeless patients should be provided with pillboxes.

Children and adolescents

-Individualised case management can improve entry into care and retention and is recommended for all younger patients.

-Pill swallowing training is recommended for children.

-Directly observed therapy can improve adherence in the short term and may be appropriate in some circumstances.

Recommendations for future research

-The impact of co-infections on adherence.

-Factors affecting adherence to antiretroviral therapy when used for the purposes of prevention.

“As the global economy contracts, the identification and implementation of evidence-based strategies to maximize the individuals and societal benefits of HIV treatment will become increasingly important,” conclude the investigators. “With proper research and resources, the tools are at hand for substantially decreasing – and perhaps ending – the global HIV epidemic.”

 

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New US Treatment Guidelines Recommend Antiretroviral Treatment for All People with HIV. 29/3/12

The new recommendations strengthen previous US recommendations on when to start treatment, which recommended initiating treatment at CD4 cell counts between 350 and 500 cells/mm3.

AIDSMap

By Keith Alcorn
29 March 2012

Newly updated US antiretroviral treatment guidelines are recommending antiretroviral treatment for all people with HIV infection, with particular emphasis on treatment for: people with CD4 cell counts below 500; anyone at risk of transmitting HIV to partners; pregnant women; and people with hepatitis B co-infection or HIV-related kidney disease.

The new recommendations strengthen previous US recommendations on when to start treatment, which recommended initiating treatment at CD4 cell counts between 350 and 500 cells/mm3. The 2009 guidelines panel was, however, divided as to the strength of this recommendation: based on available evidence, 55% of the panel considered it a 'strong' recommendation and 45% 'moderate'.

The new Department of Health and Human Services (DHHS) guidelines state that “antiretroviral therapy is recommended for all HIV-infected individuals”.

In support of this recommendation, the new guidelines cite a range of evidence showing associations between viral replication and increased risk of illness and death in people with HIV, but do not discuss the absolute reduction in risk that might be associated with earlier treatment, nor the number of people who would need to receive treatment in order to prevent one new death or event in a year.

In contrast, recently issued draft British HIV Association treatment guidelines continue to recommend treatment when the CD4 cell count falls below 350 cells, although treatment may be started earlier in people with hepatitis B or by people concerned about the risk of transmitting HIV to partners. British guidelines also recommend earlier treatment where a number of other conditions are present.

The new US guidelines draw attention to data from two large cohort studies which show that any degree of uncontrolled viral replication above 500 copies/ml, and the duration of uncontrolled viral replication, are each associated with a higher risk of death.

The guidelines also note an association between HIV infection, immunosuppression and an increased risk of cardiovascular disease and of malignancies.

They highlight the fact that older patients consistently have poorer CD4 cell responses after starting treatment, and suggest that starting treatment earlier may result in better CD4 cell responses to treatment.

In common with new recommendations in the British HIV Association guidelines, the US guidelines also discuss the new evidence from the HPTN 052 study showing that HIV treatment greatly reduces the risk of HIV transmission. This information should be discussed with all patients, the US guidelines recommend, and antiretroviral therapy should be offered to all patients at risk of transmitting HIV to their partners.

Note: This article has been amended since it was first published on March 29 after a discrepancy between between the .pdf version of the March 2012 guidelines and the HTML version of the March 2012 guidelines posted to aidsinfo.nih.gov was drawn to our attention. The erroneous information, suggesting that expert opinion was evenly divided regarding antirtetroviral treatment initiation in people with CD4 counts above 500 in the March 2012 guidelines, has been corrected here and on aidsinfo.nih.gov.

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Study Confirms Viral Load Most Important Predictor of HIV Transmission. 13/1/12

Primary goal of the study was to calculate the risk of HIV transmission per act of sexual intercourse with an HIV-positive partner in the absence of antiretroviral treatment

13 January 2012

A new African study of heterosexual HIV-serodiscordant couples—in which one partner is positive and the other is negative—confirms that viral load is the most important factor influencing the risk of transmitting the virus, according to data published in the February 1 issue of The Journal of Infectious Diseases. The findings also stress the importance of other transmission variables, including condom use, age, male circumcision status and the presence of other sexually transmitted infections (STIs).

The primary goal of the study was to calculate the risk of HIV transmission per act of sexual intercourse with an HIV-positive partner in the absence of antiretroviral treatment, notably among heterosexuals in sub-Saharan Africa, who make up roughly two thirds of the world’s population of people living with HIV. According to study authors James Hughes, PhD, of the University of Washington and his colleagues, the average rate of infection was found to be 1 per 900 coital acts.

Though estimates of the probability of HIV infection per act of sexual intercourse can be confusing on a level of personal decision making—it only takes one unsafe sexual encounter to become infected with the virus—these estimates are of importance to experts in the field of HIV epidemiology and prevention. According to an editorial accompanying Hughes and his team’s paper, Ronald Gray, PhD, and Maria Wawer, MD, of Johns Hopkins University point out that these estimates are needed “for modeling the epidemic and for projecting the effects of preventive interventions.” Indeed, they add, these estimates “[have] been the holy grail of HIV epidemiology for [more than] two decades.”

Estimates, however, haven’t been consistent, given variations in the populations included in studies, including those residing in low- and high-income countries, male-to-female versus female-to-male transmission, stage of HIV infection in the positive partner, the effects of demographic and behavioral characteristics and STI cofactors.

In an effort to provide more consistent results, Hughes and his colleagues—including researchers in eastern and southern African—analyzed data from a study that included 3,297 HIV-discordant couples in South Africa, Kenya, Rwanda and Zambia who received either acyclovir or placebo to determine the effects of suppressing genital herpes, or herpes simplex virus-2 (HSV-2) infection, on HIV transmission rates. The couples had frequent follow-up to measure viral loads in the positive partner; this included genetic testing to link the transmitted virus to the HIV-positive partner in order to prevent including infections acquired from other possible partners.

Though the study did not find an association between acyclovir use and HIV transmission, it provided the researchers with the opportunity to estimate per coital HIV transmission, considering that antiretroviral therapy was only offered once the positive partner’s CD4 cell count fell below 250.

Overall, there were one to two incidents of HIV transmission per 1,000 acts of sexual intercourse—a rate similar to those found in other low-income countries, but higher than estimates from many industrialized countries.

The viral load in the original infected partner was the main driver of transmission, with the risk increasing 2.9 times for every log increase in viral load (for example, an increase from 10,000 copies to 100,000 copies). This finding was somewhat higher than previous estimates of transmission risk associated with viral load, possibly because the short follow-up intervals and frequent viral load measurements in the study allowed more precise estimates of the association between HIV levels and infectivity.

The study also confirmed that condoms are highly protective, reducing the risk of HIV transmission by 78 percent when volunteers self-reported condom use. “[This] suggests a very high rate of consistent use, which is atypical for married couples in sub-Saharan Africa,” Gray and Wawer note. 

Older age was also associated with reduced transmission per sex act, as has been previously reported, and male circumcision reduced female-to-male transmission by about 47 percent, an effect compatible with the efficacy reported in three randomized trials of circumcision for HIV prevention.

HSV-2 infection and genital ulceration increased transmission between 2 and 2.7 times, another confirmation of previous research findings.

The findings also showed that the risk of an HIV-positive man transmitting the virus to a negative woman was about twice the risk of an HIV-positive woman transmitting it to an HIV-negative man. However, this difference can be attributed to the difference in viral loads between men and women, the authors noted. After adjusting the data for viral load differences—the men in the study tended to have higher levels, on average—the male-to-female and female-to-male transmission rates per act of sexual intercourse were found to be similar. This finding differs from those in high-income countries, where the transmission risk from men to women is significantly higher, even after adjusting for viral load differences.

Differences in age and HSV-2 infection in the HIV-negative partners also help account for the gender disparity—the HIV-negative female partners were, on average, younger and had higher rates of genital herpes than their male counterparts.

“Our results underscore the importance of antiretroviral therapy”—findings underscored by the encouraging results of the HPTN 052 study—“and, possibly, treatment of coinfections, to reduce plasma HIV-1 viral load in HIV-1 infected partners, and condom promotion, male circumcision, and treatment of symptomatic sexually transmitted infections for HIV-1 uninfected partners as potential interventions to reduce HIV-1 transmission,” Hughes and his colleagues conclude.

 

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Treatment News 2011

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Depression "Overlooked" in Treating HIV Patients. 7/12/11

HIV patients in Africa frequently suffer shame and depression but the continent’s health systems are ill-equipped to handle the issue

7 December 2011

Addis Ababa - HIV patients in Africa frequently suffer shame and depression but the continent’s health systems are ill-equipped to handle the issue, which not only affects their quality of life, but can lead to poor adherence to HIV treatment regimens.

While HIV programmes focus heavily on reducing externalized stigma and ill-treatment of HIV patients by society, little is done to deal with a patients’ self-perception and how that might deteriorate following an HIV diagnosis, speakers said at a session on stigma at the 16th International Conference on AIDS and Sexually transmitted infections in Africa in Addis Ababa.

Studies show that depression is the most common psychiatric disorder among people living with HIV, and is more prevalent among HIV-positive people than the general population.

"Operational research carried out in Zambia has found a positive correlation between patients who self-stigmatized and failure to adhere to treatment," said Sikazwe Izukanyi from Zambia’s Ministry of Health. "Self-stigma was often found in patients who did not disclose their status to partners or family members - making it difficult to maintain strict adherence to regimens while trying to hide the drugs."

Izukanyi noted that while counselling was a standard part of HIV care in Zambia, counsellors needed to be made aware of the prevalence of self-stigma and how to deal with it.

A 2010 Ugandan study by Makerere University found that HIV-positive patients were more critical of themselves, had significantly greater problems making decisions, poorer sleep, tired more easily, experienced more appetite changes and had more cognitive impairment.

ARVs and self-stigma

According to a study by Yordanos Tiruneh, an Ethiopian academic with US-based Northwestern University, antiretroviral (ARV) therapy has been key to reducing external stigma by minimizing the visibility of physical imperfections and restoring functional daily activities such as the ability to work. The study, which used 105 interviews with Ethiopian men and women on ARVs, also found that the support networks formed by people living with HIV gave them much-needed social capital.

However, according to Yordanos, while ARVs were linked to a reduction in external stigma, the study found that they tended to increase internalized stigma, sometimes resulting in failure to properly adhere to ARVs.

"When I think of the two tablets that keep me alive, I hate myself and I feel that I am dead," one of the study’s interviewees is quoted as saying. "Sometimes I get furious to see myself like a walking corpse, and other times I see myself as a doll that functions with a battery. I would say, without these batteries [pills], I am nothing."

According to a US study, adherence to ARVs was higher in patients for whom anti-depressants were prescribed.

A severe shortage of mental health professionals in Africa means that HIV-associated depression is largely ignored. For instance, according to the UN World Health Organization, Burundi has just one psychosocial care provider per 100,000, against a target of at least eight, while Ethiopia has less than one, against a similar target.

"The problem is largely a human resources one; while strengthening health systems, governments should remember to focus on mental-health issues," said Izukanyi. "As it is, we have no systems for screening, diagnosing and treating patients with mental-health issues."

Among other things, experts recommend integrating mental-health services into primary healthcare activities, developing mechanisms to ensure a good supply of psychotropic medication and more research into mental-health issues in Africa.

 

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New Data backs Early HIV Treatment Cost-effectiveness. 26/9/11

Earlier HIV treatment is cost-effective, reducing the risk of death by 75 percent among HIV patients for just US$6.25 more a month

26 September 2011

Modelling has demonstrated the benefits and now data has provided the proof as researchers in Haiti have found that earlier HIV treatment is cost-effective, reducing the risk of death by 75 percent among HIV patients for just US$6.25 more a month.

In 2009, researchers released the results of a then unpublished Haitian clinical trial. Conducted among 800 HIV patients, the study showed that those who received antiretrovirals (ARVs) when their immune systems were stronger - at higher CD4 counts of 200 to 350 - were less likely to die than their peers who waited until their CD4 counts fell to 200.

About five months later, the World Health Organization (WHO) issued new HIV treatment guidelines that advised countries to start HIV patients on treatment at a new higher CD4 count of 350 instead of 200.

Now those researchers have released the world's first and possibly only cost-effectiveness study on earlier HIV treatment tied to a randomized clinical trial. Published in the September 2011 edition of the medical journal, PLoS Medicine, the study is based on data from the original Haitian study that allowed researchers to calculate costs associated with the first three years of earlier treatment - including everything from drug and family caregiver costs to subsidies for patient transport to and from the clinic.

Bruce Schackman, associate professor of public health at the US Weill Cornell Medical College and a co-author of the study, said this was probably the first and last research of its kind. Given the overwhelming evidence for early treatment, duplicating the study now would be unethical, he said.

"This was a unique opportunity to do this kind of research," Schackman told IRIN/PlusNews. "I don't think we'd be able to do a similar comparison [study] given the compelling mortality gain we've seen with early treatment."

And although cost effectiveness is relative, Schackman said he believed the findings were applicable to other countries.

"The patterns of care that occurred in the early treatment versus the standard treatment group are generalizable," he told IRIN/PlusNews.

"Among the standard treatment group, you see higher costs for lab tests and more costs for outpatient care because patients were not yet receiving drugs and got sicker."

He added that some countries with higher healthcare costs than Haiti might see an even greater degree of cost-effectiveness.

With an HIV prevalence of about 2 percent, Haiti has the second highest prevalence rate in the Caribbean. The country moved to earlier treatment at CD4 counts of 350 soon after the WHO revised its guidelines, informed in part by the Haiti study. More than half of all HIV patients in the country are under the care of the health organizations that undertook the research - the Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) and Partners in Health. 

"This study is so important because the US government pays a lot of money for HIV treatment and... right now there's a committee in Congress that is trying to cut millions in foreign aid," said lead author Serena Koenig. "Our ability to treat people in resource-poor settings depends greatly on how much it costs."

Koenig is also the medical director for Partners in Health's Haiti programmes.

Long-term benefits

Up until now, the cost-effectiveness of early treatment had only been shown through modelling studies. These have demonstrated that while earlier treatment involves more money for drugs initially, it becomes more cost-effective the longer patients are on ARVs as they stay healthier for longer, decreasing the burden on national health systems.

The median follow-up time for patients enrolled in the Haiti study was only 21 months and while 18 lives were saved by access to early treatment during this time, Koenig said she expected her research team to find early ARVs even more cost-effective as they continue to track patients for the next 10 years.

After the trial was stopped in 2009, all patients with CD4 counts of 350 or below in the study were offered HIV treatment and uptake was high, according to Koenig. However, those patients who started treatment later may never recover as much of their immune system as their early-treatment peers.

"There are indications that patients who start treatment late never develop the immune system that they would have with early treatment," she told IRIN/PlusNews. "For the rest of their lives they are going to have more infections.

"For the price of two Starbuck's lattes a month, you could preserve someone's immune system," Koenig added. "In the US, if we had an intervention that reduced mortality by 75 percent that only cost a few dollars a month? Sure, we'd do it."

Both authors said they hoped their findings would help more developing countries move towards adopting earlier treatment - and donors commit to supporting this.

"It's important to highlight the findings of this study but also to continue the funding for early treatment, which also has HIV prevention benefits that were not part of the economic analysis, as well as direct life expectancy benefits," Schackman said. "In this environment it's challenging to do that but we're hoping this will provide the additional economic [rationale] to pursue this."

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Consistent Relationship between Depression and Poor Adherence to HIV Therapy. 1/9/11

Depression has a significant impact on adherence to HIV antiretroviral therapy

AIDSMap

By Michael Carter
1 September 2011

Depression has a significant impact on adherence to antiretroviral therapy, according to a meta-analysis published in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

The results of 95 studies involving 36,000 patients were examined by investigators, who comment “depression is consistently associated with nonadherence to HIV treatment.”

Depression was associated with poorer adherence in cross-sectional and longitudinal studies, in both resource-rich and resource-poor settings, and in all populations affected by HIV.

“Interventions that target depressive symptoms and optimal utilisation of HAART [highly active antiretroviral therapy] may have maximal effects on health outcomes,” write the authors.

HIV therapy works best if all or nearly all of the recommended doses are taken correctly. However, many patients have difficulty adhering to their therapy, and poorer adherence has been associated with an increased risk of treatment failure.

Missing occasional doses of medication is usually due to simple forgetfulness and is unlikely to have any clinical significance. However, poorer adherence can be related to social circumstances or co-morbid conditions, including mental health problems.

Depression and depressive symptoms are common in patients with HIV, with some studies finding a prevalence of 36%.

Many studies have looked at the relationship between depression and poor adherence to HIV therapy, but until now there has been no meta-analysis of their results, evaluating the strength and consistency of their findings.

Therefore a team of investigators lead by Dr Jeffrey Gonzalez of the Albert Einstein College of Medicine, New York, conducted a literature search to identify studies published since 1996 that examined the impact of depression or depressive symptoms on adherence.

A total of 95 studies involving over 36,000 patients met their inclusion criteria.

Overall, the studies showed a highly significant relationship between depression and non-adherence (p < 0.0001).

The overall effect of depression on adherence was relatively modest (0.19). However, the investigators note that it was of a similar magnitude to that observed in a separate meta-analysis into the effect of depression on adherence in other chronic illnesses.

Studies that measured adherence by interview found a significantly stronger relationship between depression and non-adherence that studies employing self-completed questionnaires (p = 0.03).

Depression was equally likely to affect adherence in cross-sectional and longitudinal studies.

Even mild symptoms of depression were associated with poorer adherence, the investigators commenting, “Our findings also suggest that the relationship between depression and HAART nonadherence is not limited to comparisons between those who meet the criteria for clinical depression and those who do not…studies that focused on depression diagnosis found equivalent effects to studies that measured depression as a degree of symptom severity.”

However, the meta-analysis was not able to show how depression affects adherence.

The researchers speculate that it could be related to its impact on concentration, appetite, self-worth, or self-care.

They conclude, “novel approaches to the successful management of these linked problems could have significant public health benefits for patients living with HIV/AIDS."

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HIV/AIDS - Double the Number of People on ARVs. 25/8/11

Reduced international drug prices have enabled the South African health department to provide antiretroviral (ARV) treatment to more people with HIV/AIDS

25 August 2011

Reduced international drug prices have enabled the health department to provide antiretroviral (ARV) treatment to more people with HIV/Aids.

In December 2010 the department saved R4,7bn (53%) on its R8,8bn, two- year ARV bill — the world’s biggest — and this month it saved a further R75,3m (14,6%) on its R485m bill for tuberculosis drugs.

The lower drug prices were supported by greater competition and globally reduced prices of active pharmaceutical ingredients.

Anban Pillay, health department cluster manager for financial planning & health economics, says an additional R8bn, over three years, became available on top of the current R11,4bn allocated for HIV treatment.

“The reduced prices meant we could afford to double the number of people now on treatment,” Pillay says. “International evidence suggests that earlier initiation of ARV treatment lowers morbidity and mortality rates.”

There are an estimated 5,6m HIV- positive people in SA, with only 1,4m on the state’s ARV programme. Government wants to increase this to 3,6m by 2015.

Last week, deputy president Kgalema Motlanthe announced that all HIV/Aids patients with a CD4 count of below 350 would receive ARVs. Previously, ARV treatment started at a CD4 level of 200, when patients are weaker .

A CD4 count is a measure of cells in the blood that reflect the health of the immune system; a declining count indicates HIV progression. Experts believe early ARV treatment can extend life expectancy by up to 25 years.

Starting at the 350 CD4 level is also in line with World Health Organisation guidelines.

Government last December extended ARVs to pregnant mothers, HIV-positive babies and patients with an HIV/TB co- infection with a CD4 count of 350.

A Médecins sans Frontières study in Lesotho found that patients who started treatment above the 200 CD4 count were 68% less likely to die and 39% less likely to be lost to follow-up treatment than patients who started treatment at below 200.

Since the introduction of ARV treatment in 2004, life expectancy for SA females has increased from 50 to 55 years, and male life expectancy from 45 to 54 years.

Médecins sans Frontières’ deputy head of mission in SA, Lynne Wilkinson, has expressed “relief” that SA is adopting and implementing WHO guidelines for treatment. “We hope people who have been waiting for their CD4 counts to drop below 200 no longer need to take this risk, and we can focus our attention on increasing the uptake of ARV treatment among HIV-positive people.”

Treatment Action Campaign spokesman Caroline Nenguke says the organisation hopes government will initiate ARV treatment for HIV patients with TB regardless of their CD4 count.

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ARV Programme now Open to All. 12/8/11

South Africa: All HIV patients with a CD4 count of 350 or less will now get government antiretroviral (ARV) treatment

12 August 2011

Bloemfontein - All HIV patients with a CD4 count of 350 or less will now get government antiretroviral (ARV) treatment, Deputy President Kgalema Motlanthe announced on Friday.

Motlanthe chaired a South African National Aids Council (Sanac) meeting, where the announcement was made in Bloemfontein.

Health Minister Aaron Motsoaledi said in 2009 the treatment for patients with a CD4 count of 350 was open only to certain “vulnerable” sections of the society such as pregnant women and children.

“Everybody who is HIV positive, regardless of what category they fall in, as long as their CD4 count is 350 they would start treatment.”

Replying to questions, Motsoaledi said the new move would cost the country more in ARV’s.

The government would budget R5bn for the first year with another billion rand added in the next financial year.

However, he thinks South Africa could afford the new costs as government had brought the cost of ARV medicine down by R4.7bn, an estimated 53%.

This was done with government’s new way of buying ARV medicines, which was done in a more “efficient” way.

Motsoaledi said the HCT campaign, which entailed a massive HIV counselling and testing drive which started in April 2010, was very successful.

In the past 15 months some 14 million people had been reached and 12 million people tested for HIV in the public sector and 1.5 million in the private sector.

Some two million people were found to be HIV positive and were referred for further care.

Motsoaledi said 60% of those tested in the HCT campaign were woman and more would be done to get men involved in future testing programmes.

“This is not a battle only for women, men must come on board.”

The minister also indicated that the ARV programme would be integrated into the future National Health Insurance system.

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All People with HIV with CD4 Counts below 350 are now Eligible for Antiretroviral Treatment. 12/8/11

The Treatment Action Campaign (TAC) welcomes the announcement today by South African Deputy President Kgalema Motlanthe

12 August 2011

The Treatment Action Campaign (TAC) welcomes the announcement today by Deputy President Kgalema Motlanthe that all people with HIV with CD4 counts below 350 cells/mm3 will be offered antiretroviral treatment.

Civil society has been calling for this policy change since the antiretroviral treatment guidelines were last updated. It is a measure that will improve the quality of life of many people with HIV, reduce mortality and reduce new infections. Until today, the guidelines only provided for treatment for people with CD4 counts below 350 cells/mm3 if they were pregnant or had active TB. All other patients had to wait until their CD4 counts fell below 200 cells/mm3.

The evidence for the policy change is very strong:

- A randomised controlled clinical trial in Haiti showed that a CD4 count threshold of 350 reduces deaths compared to a threshold of 200. [1]

- A study by Medecins Sans Frontieres in Lesotho found that patients who started treatment above 200 were 68% less likely to die and 39% less likely to be lost to follow-up compared to patients who initiated below 200 cells/mm3. Only a small proportion of these patients were pregnant or had active TB and would therefore have been eligible for treatment in the South African public sector until today. [2]

- A study in Masiphumelele township in Cape Town found that as more people were placed on antiretroviral treatment, the number of new TB cases dropped. [3]

- The recently published HPTN 052 trial showed that starting people on treatment earlier reduces their risk of transmitting HIV. [4]

Government has until now been concerned about the increase in the cost of the programme. An analysis by The Health Economics and Epidemiology Research Office of the University of Witwatersrand Health Consortium (HERO) presented in 2010 at the Budget and Expenditure Monitoring Forum showed that purchasing drugs at prices higher than necessary and insufficient task-shifting to nurses and counsellors are much more serious drivers of the cost of the programme than the CD4 threshold. [5] The policy change will reduce opportunistic infections, saving both patients and the health system time and money.

What next?

The World Health Organisation recommends that all HIV-positive patients with TB should start treatment irrespective of their CD4 count. Government should give serious consideration to implementing this measure.

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Only Modest Benefits from Starting HIV Therapy with a CD4 Cell Count above 500 Compared to 350. 27/6/11

Starting HIV therapy with a CD4 cell count above 500 cells/mm3 has only minimal additional benefits

AIDSMap

By Michael Carter
27 June 2011

Starting HIV therapy with a CD4 cell count above 500 cells/mm3 has only minimal additional benefits compared to initiating therapy with a CD4 cell count in the region of 350-500 cells/mm3, Australian investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

The study was restricted to patients with started antiretroviral treatment when their CD4 cell count was above 350 cells/mm3.

Patients with CD4 cell counts between 350-500 cells/mm3 rapidly achieved increases to above 500 cells/mm3. Moreover, 72 months after the commencement of treatment, patients had broadly comparable CD4 cell counts, regardless of their immune status at baseline.

Starting treatment at higher CD4 cell counts had clinical benefits, but overall these were modest.

The study will inform the ongoing debate about the best time to start antiretroviral therapy.

Individuals who start treatment before their CD4 cell count falls below 350 cells/mm3 are known to have a lower risk of illness and death from both HIV-related and some non-HIV-related diseases. However, the benefits of therapy at higher CD4 cell counts are unclear. Some doctors believe that the threshold for initiating therapy should be 500 cells/mm3.

A large randomised clinical trial called the START study is currently examining this question, but  its results are not expected for a number of years. Therefore Australian investigators performed an observational study involving 432 individuals who started HIV therapy when their CD4 cell count was above 350 cells/mm3.

The patients were stratified into three groups on the basis of their baseline CD4 cell count (350-500; 501-650; above 650 cells/mm3), and were followed for 72 months, with investigators monitoring changes in CD4 cell counts between the three groups.

Using data obtained from other large studies, the investigators calculated the impact of baseline CD4 cell strata on the risk of progression to AIDS or death.

After twelve months of HIV therapy, mean CD4 cell counts had increased to above 500 cells/mm3 for patients in all baseline CD4 cell strata (means 596, 717, and 881 cells/mm3 respectively).

“Patients who commenced treatment with a baseline CD4 cell count 351-500 cells/mm3, typically and rapidly…achieved and maintained a CD4 cell count greater than 500 cells/mm3,” comment the investigators.

After 72 months of therapy, mean CD4 cell counts were broadly comparable regardless of baseline CD4 cell strata (689, 746 and 742 cells/mm3 respectively).

The investigators then turned their attention to the impact of baseline CD4 cell count on the risk of death or AIDS.

Using data from another study, the investigators estimated that patients who started treatment when their CD4 cell count was above 650 cells/mm3 had a projected 8% reduction in mortality over 72 months compared to individuals who initiated therapy when their CD4 cell count was in the region of 350-500 cells/mm3, an absolute risk reduction of 0.33 per 1000 patient years.

Comparison with patients in the 500-650 cells/mm3 strata showed that individuals with a CD4 cell count above 650 cells/mm3 had a 4% reduction in their risk of death over six years, an absolute reduction of 0.16 per 1000 person years.

Extrapolation of data from two other studies showed that patients who started therapy with a CD4 cell count above 650 cells/mm3 reduced their risk of progressing to AIDS or death by 14% compared to individuals who initiated therapy with a CD4 cell count between 350-500 cells/mm3.

“Our results shows that potentially, initiating cART (combination antiretroviral therapy) at CD4 cell counts >650 cells/mm3 could yield the prevention of hundreds or thousands or AIDS events or illnesses,” write the authors.

They conclude, “our analysis suggests that patients who start cART at CD4 counts >650 cells/mm3 have better preserved immune function, but only to a relatively modest degree…furthermore the extent to which this might be expected to result in better clinical outcomes we show to be uncertain.”

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UNAIDS: Treat 15 million by 2015. 6/6/11

Global funding for AIDS needs to increase by one-third in the short term and by 20% in the longer term in order to achieve a radical reduction in new infections within a  decade

AIDSMap

By Keith Alcorn
6 June 2011

Global funding for AIDS needs to increase by one-third in the short term and by 20% in the longer term in order to achieve a radical reduction in new infections within a  decade, according to projections issued on June 3rd by UNAIDS

UNAIDS executive director Michel Sidibé told reporters ahead of this week’s UN General Assembly Special Session on AIDS, that UNAIDS was pushing world leaders to commit to a target of treating 15 million people by 2015, and to a major increase in funding in order to decisively alter the course of the epidemic over the next decade.

The agency also reported that 6.6 million people worldwide are receiving antiretroviral treatment, with 1.4 million people starting treatment in 2010 alone.

UNAIDS estimates that 34 million people are living with HIV worldwide.

According to the AIDS at 30 report, the global rate of new HIV infections declined by nearly 25% between 2001 and 2009. In India, the rate of new HIV infections fell by more than 50% and in South Africa by more than 35%; both countries have the largest number of people living with HIV on their continents.

However UNAIDS also reported that funding for HIV prevention, treatment and care fell for the first time in 2010.

“I am worried that international investments are falling at a time when the AIDS response is delivering results for people,” said Mr Sidibé. “If we do not invest now, we will have to pay several times more in the future.”

A highly detailed modelling exercise led by the World Health Organization suggests that an increase in funding of one-third between now and 2015, coupled with a much tougher approach to funding only what is known to work, could avert 12.2 million new HIV infections over the next decade.

What UNAIDS and WHO call an investment framework is led by the principles of `know your epidemic and know your response`, and seeks to channel funds in a much more rigorous way towards interventions that are known to work, and towards populations at greatest risk of infection.

The modelling work found that the most targeted approaches were likely to have biggest impact on new infections. For example, a comparison of a `broad and shallow` or a `narrow and deep` programme in KwaZulu-Natal, South Africa, found that achieving 80% coverage of antiretroviral therapy and circumcision of 70% of uncircumcised men had a substantially greater effect on HIV incidence over ten years than a wider programme that also sought to increase condom use, counsel individuals on risk reduction and promote microbicide use in women, all at low levels. The `broad and shallow` approach assumed much lower levels of treatment access and circumcision.

The impact of a `narrow and deep` approach was even more profound in Karachi, Pakistan, where a highly targeted approach that focussed on 80% treatment coverage and 80% access to needle exchange and opioid substitution had a much greater impact on new infections than a broad approach which delivered lower levels of treatment and harm reduction alongside behaviour change interventions.

The `narrow but deep` approach might reduce new infections in Karachi by over 80% within six years, the modelling exercise concluded.

However, the researchers are not advocating that all countries follow this approach; the allocation of resources is highly dependent on the epidemiological context.

The model estimated resource needs for 139 countries based on epidemiological data and information on current coverage of prevention, treatment and care.

The model showed that if applied across all countries, global resource needs would rise from the current need of $16 billion per year to peak at $22 billion in 2015, before beginning to fall back gradually as a result of economies of scale and a decline in new infections.

Requirements for the core programme activities – treatment and care, condoms promotion and distribution, prevention of mother to child transmission, male circumcision and behaviour change programmes – rises from $7 million in 2011 to $12.9 billion in 2015 and then falls back to $10.6 billion in 2020.

This costing assumes that 13.1 million of the 18.3 million people eligible for treatment will be receiving it by 2015, and 18.7 million by 2020.

Expanding treatment to provide antiretrovirals to all HIV-discordant couples where the partner with HIV has a CD4 count between 350 and 550 – the group studied in the recently announced HPTN 052 study – would increase the number in need of treatment by 1 million in 2015, and would add $500 million to the cost of the framework package by 2015.

New infections are predicted to decline from about 2.4 million in 2011 to 1 million in 2015 and 870,000 a year in 2020. The new framework could avert 12.2 million new infections between 2011 and 2020, including 1.9 million in infants. In addition, expansion of treatment would avert 7.4 million deaths over the same period. Treatment for HIV-discordant couples above the currently recommended threshold for starting treatment would avert an estimated 340,000 infections.

The researchers estimate that the cost per-life year gained of the interventions in the framework is $1060, making it affordable for even the poorest countries. Any health intervention which costs less than the GDP per capita of a country is judged highly cost-effective by the World Health Organization.

The massive expansion in treatment numbers would be facilitated by community mobilisation and by large reductions in the cost of drugs and treatment delivery, the authors say. In particular the model assumes that previous cost reduction trends will continue, allowing a 65% reduction in the cost of treatment between 2011 and 2020. A shift towards delivery of antiretroviral treatment through primary care and community-based care will be critical in achieving the cost reduction.

But reluctance is being expressed by the governments of wealthy country governments to sign up to new targets for treatment expansion at this week’s UNGASS meeting.

Furthermore, activists monitoring the negotations on a final declaration say that wealthy countries are also trying to water down any commitment to improve access to medicines in the final statement.

“We are seeing an unusual position being taken by the EU which is refusing to commit to any treatment targets and at the same time is working with the US to remove or significantly dilute any language in the text related to increasing access to safe, effective and affordable generic medicines,” said Matthew Kavanagh of Health GAP (Global Access Project).

Language proposed by the nations facilitating the UN process, Botswana and Australia, on trade agreements and the removal of any and all TRIPS-plus measures from free trade agreements has been rejected by the EU. They are joined in this by the United States and Japan.

TRIPS-plus measures seek to enforce higher standards of intellectual property protection on developing countries as the price of access to the markets of the wealthiest nations. These measures may undermine opportunities to use TRIPS flexibilities that allow low and middle-income countries to manufacture and / or export antiretroviral drugs that are still patented in wealthy countries.

These measures may stand in the way of manufacturing new antiretroviral combinations that are cheap, less toxic and less prone to drug resistance, and may also choke off the supply of cheap drugs for second-line antiretroviral treatment in those whose first drug combination has failed to control HIV.

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Drug Price Cuts Secured Amid Growing Funding Fears. 19/05/11

Reduction in ARV costs will save millions.

JOHANNESBURG, 19 May, 19 (PLUSNEWS) - Three international organizations have negotiated reductions on key first- and second-line, and paediatric antiretrovirals (ARVs) that will help countries save at least US$600 million over the next three years. 

The Clinton Health Access Initiative (CHAI), the international drug purchasing facility UNITAID and the UK Department for International Development (DFID) made the announcement on 18 May. 

The deal, expected to affect most of the 70 countries comprising CHAI's Procurement Consortium, features notable reductions in the prices of tenofovir (TDF), efavirenz, and the second-line ritonavir-boosted atazanavir (ATV/r) used in HIV patients who have failed initial, or "first-line", regimens. 

As part of the deal, the three bodies set price ceilings for more than 40 adult and paediatric ARVs with eight pharmaceutical manufacturers and suppliers, including Cipla Ltd, Matrix Laboratories and Autobindo Pharma.

Together these eight companies account for most ARVs sold in countries with access to generic drugs, according to David Ripin, scientific director of CHAI's Drug Access Programme. 

As a result, the cost of ATV/r is down by two-thirds from just three years ago. Meanwhile, a once-a-day fixed-dose combination (FDC) pill containing TDF and efavirenz will now cost countries less than US$159 per patient per year. In 2008, low-income countries paid about $400 per patient per year for the same pill. 

How did they do it? 

According to UNITAID and CHAI, this success is a product of increased demand for these drugs and more efficient manufacturing of the active ingredients, which are estimated to account for as much as 75 percent of generic ARV costs.

"When you make an active ingredient, you use a multistep chemical process," Ripin told IRIN/PlusNews. "To reduce costs, you can look for a less expensive source of raw materials of which there are a few examples, including TDF ... or you can tinker with the chemical process used to make the product to make them more efficient." 

But Ripin added that doing either comes at a cost for pharmaceutical companies, for whom a change in raw material suppliers or manufacturing processes means re-applying for approval of the drug with regulatory bodies. 

"Any time you change anything with the way you make a drug, you need to get regulatory approval," he said. "You have to do a fair amount of work to prove that your product works just as well now as it did before. 

"The pharmaceutical companies and generic manufacturers are fantastic at making these types of improvements. [but] they have a limited set of research and development resources available to them," Ripin said. "They often need to make a decision where they are going to get a higher return on that research and development, and typically that comes from the introduction of new products on the market." 

According to Ripin, the key is providing companies with data on the large and growing markets for ARVs. 

"We help companies evaluate for themselves whether it's a worthwhile business opportunity," he said. "The second key factor they have to consider is the competitive marketplace for their drugs, where there is an incentive for lower [production] costs and lower-priced products as they want to maintain their market share." 

CHAI also provides countries with data on best market prices for drugs to help inform national procurement, as was the case with South Africa's recent ARV tender.  Although South Africa is not expected to benefit from the new price cuts, the country has the largest ARV tender in the world, and could secure the drugs at competitive prices. In terms of the CHAI agreement, lower prices are available to members of the Procurement Consortium but are dependant on volumes ordered.

How low can we go? 

TDF has become an important drug for many countries, including South Africa, hoping to implement the 2009 World Health Organization (WHO) HIV treatment guidelines, which recommend starting HIV patients on treatment sooner but also a shift away from more toxic ARVs to TDF. 

However, the high cost of earlier treatment and better drugs has prohibited many countries from fully implementing the WHO recommendations. According to a recent report released by Médecins Sans Frontières (MSF), both Malawi and Zimbabwe reversed their move to WHO guidelines due to financial constraints.

While new price reductions bring TDF's price closer to that of the long-time and widely adopted first-line ARV Zidovudine, further drops in TDF's price will have to be logged to ensure widespread uptake, said Brenda Waning, coordinator of market dynamics for UNITAID. 

For Waning and others like MSF, the issue of sustainable funding for the HIV response looms large ahead of the June UN meeting on HIV/AIDS in New York, rumoured to be the last for years to come, according to MSF's report.

"There has been a lot of attention on commodities and not at other major drivers of cost," she told IRIN/PlusNews. "We have to look at other places in the health system where we can capture cost-effectiveness." 

In particular, Waning pointed to the potential savings associated with the roll-out of new point-of-care diagnostics, which, although not high on the global agenda, will help countries task shift such testing away from scarce doctors.  

Although the cost remains high, introducting FDC would help governments save on ARV shipping, transportation and storage, while improving adherence and patient outcomes.

 

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Starting HIV Treatment when CD4 Cell Count Dips below 500 Improves AIDS-free Survival. 21/4/11

Patients who start antiretroviral therapy when their CD4 cell count dipped below 500 cells/mm3 are less likely to develop an AIDS-defining illness

AIDSMap

Michael Carter
21 April 2011

Patients who start antiretroviral therapy when their CD4 cell count dipped below 500 cells/mm3 are less likely to develop an AIDS-defining illness than individuals who start treatment with a CD4 cell count of 350 cells/mm3, an international team of investigators report in the Annals of Internal Medicine.

However, initiating HIV treatment with a CD4 cell count of approximately 500 cells/mm3 did not reduce the risk of all-cause mortality.

“If the goal is to prevent AIDS-defining illness or death, our findings support cART [combination antiretroviral therapy] initiation once the CD4 cell count decreases below 500 cells/mm3,” comment the investigators.

Importantly, the investigators did not gather information on the impact of earlier treatment on the risk of serious, but non-fatal, non-AIDS related illnesses.

The authors of an accompanying editorial suggest that the results of the study should be treated with “caution,” and that doctors should have “frank conversations with their patients about what we do and what we don’t know about starting cART.”

Nevertheless, results of the study will undoubtedly inform the debate about the best time to start antiretroviral therapy.

Treatment guidelines in Europe currently recommend that AIDS-free patients should start therapy when their CD4 cell count is in the region of 350 cells/mm3. However, US guidelines advocate treatment when an individual’s CD4 cell count falls under 500 cells/mm3.

Large randomised trials are currently underway to try and determine the optimum time to start HIV therapy. However, their results are not expected for several years. Because of this continuing uncertainty investigators from the HIV-CAUSAL Collaboration undertook a prospective observational study involving approximately 21,000 adult patients enrolled in cohorts in Europe and the US.

All the patients had a CD4 cell count above 500 cells/mm3 when they entered the study, and none had developed an AIDS-defining illness. The patients were recruited between 1996 and 2009. At the time of entry to the study, the patients had a median CD4 cell count of 660 cells/mm3.

The risk of all cause mortality and the risk of AIDS-related illness or death was compared between patients who started HIV treatment when their CD4 cell count was 500 cells/mm3 or above; between 350-499 cells/mm3; 200-349 cells/mm3; and below 200 cells/mm3.

A total of 390 patients developed an AIDS-defining illness or died before their CD4 cell count fell below 500 cells/mm3. HIV therapy was started by 2893 patients when their CD4 cell count was above 500 cells/mm3, and 9296 maintained a CD4 cell count above this level without the need for treatment.

The remaining 8292 patients experienced a fall in their CD4 cell count to below 500 cells/mm3 after a median of nine months.

There was no evidence that starting HIV therapy at CD4 cell counts around 500 cells/mm3, or 350 cells/mm3 significantly reduced the risk of all-cause mortality compared to initiating treatment at a CD4 cell count of 200 cells/mm3. This was equally low for all patients.

However, there was clear evidence that starting therapy at higher CD4 cell counts reduced the risk of AIDS-related illnesses or death.

Compared to patients who started treatment when their CD4 cell count fell below 500 cells/mm3, individuals initiating therapy when their CD4 cell count was below 350 cells/mm3 were 38% more likely to develop AIDS (hazard ratio [HR], 1.38; 95% CI, 1.23-1.56). Furthermore, patients who first took therapy when their CD4 cell count was below 200 cells/mm3 were 90% more likely to develop an AIDS-defining illness (HR = 1.90; 95% CI, 1.67-2.15).

Five-year survival rates were 98% for patients with a CD4 cell count around 500 cells/mm3, 98% for patients with a CD4 cell count around 350 cells/mm3 and 97% for individuals with a CD4 cell count of approximately 200 cells/mm3. AIDS-free survival rates were 92%, 92% and 88% respectively.

The investigators calculated that “approximately 48 patients would need to initiate cART when their CD4 cell count decreased below 500 cells/mm3 rather than 350 cells/mm3 to prevent 1 new case of AIDS-defining illness or death during the first 5 years.”

They add, “however, we estimated little change in all-cause mortality rates between the 500-350 threshold.”

Heart, kidney, and liver disease are now important causes of illness among people with HIV. The investigators acknowledge that a limitation of their study was lack of information on “serious nonfatal events other than AIDS-defining illnesses.”

The authors of the accompanying editorial comment that the study “is a robust, carefully performed analysis that supports the presence of a graded benefit of cART even when the risk for AIDS is low.”

However, they add, “the continuing HIV epidemic and tightening of resources requires that we clarify the absolute benefits, risks and costs of expanding the indications for cART.”

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HIV Study Claims One in Eight Children Resistant to Drugs. 20/4/11

First major study of young people with HIV questions the suitability of anti-retroviral drugs for young sufferers

The Guardian.co.uk

By Sarah Boseley
20 April 2011

One in eight children born with HIV becomes resistant to the three main classes of drugs used to suppress the virus within five years of starting treatment.

The first major study of drug resistance in young people, which looked at 1,000 European children born with HIV, raises questions about the suitability of anti-retroviral drugs for the young.

Drugs fail because the virus becomes resistant to them. This can happen if people take them erratically or stop taking them. Resistance sets in with adults, but more slowly.

But part of the problem, say Nathan Ford and Alexandra Calmy, is that the drugs available are not tested on children or turned into formulations that are easy for children to take. The doctors work for Médecins sans Frontières, which treats some of the 2 million children living with HIV, who were infected during childbirth – most of them in the developing world. Half of the children born with HIV die before their second birthday, they point out.

Even in the US and Europe, drugs for children with HIV are limited. "Of the 22 antiretroviral drugs currently approved by the US food and drug administration, five are not approved for use in children and six are not available in paediatric formulations," they write in a commentary published with the study in the Lancet medical journal.

"Additionally, treatment has to be constantly adjusted for bodyweight, and most paediatric antiretrovirals are formulated as syrups (often in large volumes) which are difficult to administer and store." Some of the drugs, they add, "are extremely unpalatable".

Half of the children born with HIV already die before their second birthday, they point out. To give more children a chance of staying alive, fixed-dose combinations of a three-drug cocktail are needed, in tablet form. They call on "drug developers, clinical trial investigators and drug regulators" to prioritise the production of better HIV drugs for children.

The study was carried out mostly in the UK, Ireland, Spain, the Netherlands and France, with smaller numbers also from Denmark, Italy and Belgium. The children were all younger than 16 and had started treatment with three or more drugs between 1998 and 2008.

The failure rate in the three main classes of drugs – known as nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), and protease inhibitors – was 12% within five years of starting. There were problems even with young children, where the parent or carer would be responsible for giving the medicine, but the failure rate was higher in older children.

"Drug adherence is a challenge for children and young people with any chronic disease. For those with HIV infection, there are additional factors, including coming to terms with disclosure of their HIV status, secrecy and guilt among adult family members and dealing with HIV alongside their own sexual development. Fear of stigma increases their isolation and tendency towards denial, all of which might adversely affect drug adherence."

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Counselling, Not Alarm Device, had Best Effect on ART Adherence. 13/4/11

Patients in Nairobi, Kenya getting intensive early adherence counselling when starting antiretroviral therapy were 29% less likely to have poor adherence

AIDSMap

Keith Alcorn
13 April 2011

Patients in Nairobi, Kenya getting intensive early adherence counselling when starting antiretroviral therapy were 29% less likely to have poor adherence and 59% less likely to have virological failure compared to those getting no counselling Michael H Chung and colleagues reported in a randomised, controlled trial published in the March issue of PLoS Medicine.

The positive effects of counselling on adherence were seen immediately after starting antiretroviral therapy and maintained throughout the18 month follow-up period.

Use of an alarm device had no effect on adherence or virological outcomes.

Public health concerns that scale-up of antiretroviral treatment in sub-Saharan Africa would lead to poor adherence and widespread drug resistance have been proven wrong, note the authors.

They cite a recent meta-analysis of 27 cohorts from 12 African countries where adequate adherence was seen in 77% of subjects compared to 55% among 31 North American cohorts.

Choice of treatment regimen may also affect drug resistance development. In most resource-poor settings antiretroviral treatment regimens include non-nucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs remain in the blood for weeks after a single-dose. This means that patients on NNRTI-containing regimens may not experience resistance unless adherence drops below 80%.

Comprehensive HIV treatment and care programmes in sub-Saharan Africa that include adherence interventions are dealing with increasing financial constraints and limited resources.

So effective delivery of services requires identifying cost-effective interventions. While adherence counselling and cheap alarm devices are in widespread use limited evidence exists of their effectiveness.

The authors chose to compare the effect of counselling and the use of an alarm device on adherence and biological outcomes in a resource-poor setting.

Between May 2006 and September 2008 400 newly-diagnosed patients, aged 18 and over, starting free antiretroviral treatment at the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya were randomised to one of four arms: Counselling; alarm device; counselling and alarm device; and neither counselling nor alarm device.

Of the 400, 362 started ART (fixed dose combination pills: stavudine [d4T], lamivudine [3TC] and nevirapine) and 310 completed the 18 month follow-up.

Blood was taken at enrolment for baseline CD4 cell counts and viral load. Blood was then drawn at six, 12 and 18 months after starting ART. Patients went to the clinic monthly with their pill bottles. The pharmacists counted and recorded the number of pills remaining and refilled the prescription. Those with an alarm device were asked about use of the device and answers recorded. Defective or lost devices were replaced.

Over two-thirds were female with a median age of 36 (IQR:31-42). The median monthly rent was US$28 (IQR: 11-56), the median distance from home to clinics was 10 kilometres (IQR: 6-15), and 10% had ever given or received money/favours in exchange for sex.

The study found a significant association between a behavioural intervention (adherence counselling) and adherence and virological impact.

Those participants getting intensive adherence counselling were 59% less likely to experience viral failure (HIV-1 RNA ≥5000 copies/ml) (HR 0.41; 95% CI: 0.21-0.81, p=0.01).

Participant getting intensive counselling were also 29% less likely to experience poor adherence <80% (HR 0.71; 95% CI: 0.49-1.01, p=0.055)compared to those getting no counselling.

There was no significant effect on poor adherence (HR 0.93; 95% CI: 0.65-1.32, p=0.7) or viral failure (HR 0.99; 95% CI: 0.53-1.84, p=1.0) when using an alarm compared to not using an alarm.

This suggests, contrary to other findings, reminding patients when to take medications may not be the primary barrier to adherence. Use of cell phones, they add, may provide patient support rather than a reminder.

Neither counselling nor use of an alarm device had any significant effect on death rates or CD4 cell counts.

Dedicating time, the authors note, on communication about adherence possibly strengthens a provider-patient relationship, improving adherence through trust. Treatment failure is substantially reduced as this study demonstrates.

An intervention that reduces viral failure by over half provides significant cost savings, they add. Costs of going on to more expensive second-line are delayed and the potential costs of treating opportunistic infections eliminated.

Limitations include a possible bias toward poorer patients according to an analysis comparing those lost to follow-up and those who were retained.  Such patients could be more receptive to attentive counselling and free medications, note the authors.

Pill counts may overestimate adherence since missing pills may not have been taken but thrown away, shared or lost.

The authors conclude “as antiretroviral treatment clinics expand to meet an increasing demand for HIV care in sub-Saharan Africa, adherence counselling should be implemented to decrease the development of treatment failure and spread of resistant HIV.”

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HIV/AIDS: Five Ways to Improve Adherence to ARVs. 13/4/11

Less-than-strict adherence undermines the efficacy of the drugs.

PlusNews
13 April 2011

Nairobi - Antiretroviral treatment has given millions of people around the world - six million at last count - a new lease on life. However, less-than-strict adherence undermines the efficacy of the drugs.

Some common reasons for failing to stick to ARV regimens include: side-effects; insufficient food; long distances and high transport costs to and from drug collection points; forgetting to take them; stigma and fear of disclosure of one's status and spending time away from home.

Adherence is crucial to preventing the huge expense of putting patients on second- and third-line HIV treatment. Here are some ways HIV programmes can improve adherence:

Continuous counselling - Crucial to ensure patients understand the importance of strictly adhering to their medication and make healthy lifestyle choices. Many HIV programmes offer counselling at the initiation of ART, after which patients merely collect their drugs from the pharmacy monthly, being seen a few times a year or only when they have other health conditions.

However, experts recommend sustained ART adherence counselling to achieve the best results. A randomized controlled study published in 2011 and conducted in the Kenyan capital, Nairobi, found that patients who received intensive counselling at the start of ART were 29 percent less likely to have poor adherence and 59 percent less likely to have virological failure compared with those who did not.

Additional lifestyle counselling, such as alcohol counselling for heavy drinkers, can also improve adherence.

Community support - Visits by community members to encourage patients to adhere to their medication, home-based care by community health workers or people visiting the clinic with the patient and keeping tabs on them between visits, can all help.

Some programmes are using community drug distribution to bring health services closer to remote villages. One Tanzanian project uses community-based volunteers - many of them HIV-positive - and trained medical workers to drive around villages refilling prescriptions and providing counselling and support to patients.

A 2011 South African study found community-based adherence to be crucial in ensuring that patients remained in care, regularly picked up their treatment and retained low viral loads.

Task-shifting - Patients do not waste precious working hours and lose money waiting for medical care. Many African countries lack medical staff; overburdened health workers are unable to provide the proper attention to patients. Task-shifting - the use of mid- to low-level health workers rather than doctors to prescribe ART - helps ease the burden on doctors and saves patients’ time.

As more HIV programmes take on task-shifting, experts warn that ongoing training and monitoring are necessary to ensure the quality of care is not compromised.

Technology - Many health centres provide patients with devices such as pill boxes, medical calendars and alarms to help them to remember to take their drugs at the appropriate time.

The use of text messages to remind patients to take their medicines and to report health issues to medical personnel is proving popular and effective. A 2011 study of 431 patients at a rural Kenyan clinic found that 53 percent receiving weekly SMS reminders achieved adherence of at least 90 percent during the 48 weeks of the study, compared with 40 percent of participants who did not.

Social assistance - Patients often abandon their HIV medication due to hunger; for others, the costs associated with travelling long distances to seek treatment are simply too high.

According to a 2010 study in Haiti, food assistance was associated with improved clinic attendance and adherence to ART, while a 2010 Ugandan study found that cash transfers of between US$5 and $8 for transport costs resulted in improved ART adherence and retention in care.

Researchers argue that the cost of food assistance and transportation is dwarfed by the potential costs - including hospitalization and additional medication - associated with failure to adhere.

 

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Concern over Theft of ARVs. 4/4/11

Civil society organisations want to see government taking a firmer stand to stop antiretroviral drugs (ARVs) from being smuggled into the black market.

Health-e

Ayanda Mkhwanazi
4 April 2011

Civil society organisations want to see government taking a firmer stand to stop antiretroviral drugs (ARVs) from being smuggled into the black market.

Government needs to take the theft of anti-retroviral drugs or ARVs seriously as people’s lives are at risk. This is according to the Treatment Action Campaign (TAC) and the National Association of People Living with AIDS (NAPWA). They say reports in the media of ARVs found on the black market are quite disturbing. As a result, many HIV-positive people are now afraid to go fetch their treatment from public health facilities for fear of being victims of people stealing their medicine.

“There are a number of people right now coming to us who have told us that they are scared to go to public healthcare facilities to get ARVs because they might be hijacked or robbed. Just last week in Hillbrow, a woman was mugged by a gang and they took her ARVs. This means it will have a huge impact on people living with HIV. In the long run they will default on treatment and develop drug resistance. Now, that is lethal. But, the main major impact is that the government’s treatment programme will fall flat”, says NAPWA’s Secretary-General, Nkululeko Nxesi.

In a recent incident three men were arrested for allegedly being in possession of ARVs to the value of R200 000. It is still unclear as to where the drugs were being taken to and what were they going to be used for. However, police have not ruled out the possibility that the drugs were going to be used and sold for whoonga.

Whoonga is a drug that has become a growing concern in the country. It is a detergent powder mixed with rat poison and crushed-up ARVs, then smoked. Nxesi says Napwa’s concern is that people are getting away with stealing crucial treatment of AIDS patients to make a quick buck.

“Government will respond very late. That is our worry. At that time how many people would have died? And how many people would have become millionaires by selling ARVs? Our call to government is that they should not use the lab experts who investigate the ingredients of whoonga. They must go where people are. Since they believe it is not true that ARVs are used for whoonga, then why was that woman in Hillbrow mugged? What about those policemen who stole ARVs... why did they do that? Who is their supplier and who is their market?” asks Nxesi

The Treatment Action Campaign has also added its voice to the matter. Last week, the TAC held a picket outside the Kempton Park Magistrates’ Court where the three men accused of stealing ARVs appeared.

“We are very worried because we know our history and how far we’ve come for people to access ARVs. People who are HIV-positive are very angry and scared because this treatment is our life.  Once you start it, you take it till death. It is like you are married to it because you take it with you everywhere you go. We are worried because if people are stealing our treatment, how can we live without them as it is a life time commitment?” said Portia Serote, deputy chairperson of the TAC in Ekhuruleni.

Meanwhile, the Gauteng Health Department says it has strict security measures in place at all of their public health pharmacies to ensure that theft of medicines is minimal. Policy Specialist at the department, Rose Mashile, says when the stock arrives at their hospitals it is thoroughly checked. Mashile says access inside the pharmacies is also controlled.

“Only pharmacy personnel are allowed into the pharmacy. You can’t go in. Even if you are working in the hospital, you will not be allowed. There are electronic controlled systems in most of our pharmacies, like swiping cards and using the finger print system. This is to protect the staff in the pharmacy. Even at dispatch, only one person is served at a time for confidentiality and security”.

But what confidentiality and security do patients really have when they are easy prey for criminals who want their antiretroviral medicines once they leave the health facilities?  Meanwhile, the TAC and NAPWA say they have begun encouraging people to collect treatment in groups for safety, and to get family members to accompany them where possible.

 

 

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Big Pharma Shows Willingness to Pool HIV/AIDS Drug Patents. 10/2/11

Cheap new combinations are going to be vital in the fight to keep millions alive in the developing world

10 February 2011

HIV/Aids may be slipping off the news agenda - see the Kaiser Family Foundation report on global health journalism, which is here - but the determined bunch of people who have got the patent pool for Aids drugs up and running are not only quietly working away, but getting results.

Not long ago there were those who doubted whether the Geneva-based Medicines Patent Pool would manage to persuade any of the big pharmaceutical companies that it was a reasonable idea to allow their patents on Aids drugs to be "pooled". Unitaid, which works to improve access to medicines in developing countries and set it up, argued long and hard that the pool was necessary. It would allow generic manufacturers in countries like India and China to make legitimate cheap combinations of some of today's advanced HIV medicines. Cheap new combinations are going to be vital in the fight to keep millions alive in the developing world as HIV inevitably develops resistance to the basic drugs now available in poor countries.

But today, two months after sending out letters inviting the major makers of Aids drugs to get involved, the patent pool announced that it is in negotiations or preparing to enter negotiations with F. Hoffman-La Roche, Gilead Sciences, Sequoia Pharmaceuticals, and ViiV Healthcare (a joint venture of GlaxoSmithKline and Pfizer). The big surprise for the sceptics is Viiv. GSK (which has far more Aids drugs than Pfizer) had appeared uninterested in the concept. Its chief executive Andrew Witty, while committed to improving access to its medicines in poor countries, said they were taking other routes.

Obviously an interest in negotiations is not the same thing as agreeing to licence your drugs for pooling purposes, but Viiv has taken the first step. The patent pool has listed all the companies it has approached on its website here, and in a nice touch, has put up the letters from those that are, shall we say, less than enthusiastic. The table will be updated every quarter. It will be worth watching.

 

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HIV Infection 'Bonus' for Whoonga Addicts. 6/2/11

HIV infection allows access to the antiretroviral (ARV) drugs used in the Whoonga

News24

By Lucus Ledwaba
6 February 2011

Johannesburg - For youths addicted to whoonga, an HIV infection is a “bonus” because it gives them access to the antiretroviral (ARV) drugs used in the mixture.

The drug efavirenz, which is prescribed under its brand name, Stocrin, to HIV-positive patients on ARV treatment, is one of the ingredients used to make whoonga.

Vumani Gwala runs Project Whoonga, a community organisation aimed at educating youths in KwaDabeka and Clermont near Durban about the dangers of drugs.

Clermont has been identified as the township with the highest prevalence of whoonga use and addiction in the country. Whoonga is sold there for as little as R20 and is popular among the 15, 16 and 17-year-old age group.

Gwala said its widespread use had led to a dramatic increase in crime in the township.

“To the addicts it’s a matter of life and death to get the drug. It does not matter how they get it,” he said.

Carol du Toit of the SA National Council on Alcoholism and Drugs in Durban said there had been a steady increase in whoonga use in the past six months.

Du Toit said although Stocrin had been widely used in whoonga in the past two years, it now appeared heroin was fast becoming the more popular choice.

She said whoonga sellers targeted economically depressed areas like informal settlements and townships with high unemployment and poverty levels.

Gwala said whoonga street sellers were very often “poor youth in the community and the best place for them to do business is schools. So our aim is to go to schools and teach about drugs. Basically we want to get to the child before the drug dealers do,” she said.

Still, Du Toit pointed out that while drugs like whoonga, nyaope and tik were a menace, alcohol still remained the ­biggest problem among South African youths.

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Intensive Adherence Counseling with HIV Treatment Improves Patient Outcomes. 1/3/11

reduction in poor adherence and virologic treatment failure

1 March 2011

Intensive adherence counseling around the time of HIV treatment initiation significantly reduces poor adherence and virologic treatment failure in sub-Saharan Africa whereas using an alarm device has no effect, according to a study in this week's PLoS Medicine by Michael Chung from the University of Washington, Seattle, USA, and colleagues.

The findings of this study define an adherence counseling protocol that is effective; these findings are relevant to other HIV clinics caring for large numbers of patients in sub-Saharan Africa.

As poor adherence to HIV treatment can lead to drug resistance and inadequate treatment, it is necessary to identify interventions to improve adherence that are inexpensive and proven to be effective in resource-limited settings. The authors randomised 400 patients who were newly diagnosed with HIV and had never before taken antiretroviral therapy to receive adherence counseling alone; alarm device alone; both adherence counseling and alarm device together; and a control group that received neither adherence counseling nor alarm device.

Patients had baseline blood taken to test for HIV-1 RNA and CD4 count and blood was then taken every 6 months for the duration of the study (18 months). After starting HIV treatment, patients returned to the study clinic every month with their pill bottles for the study pharmacist to count and record the number of pills remaining in the bottle.

Patients receiving adherence counseling were 29% less likely to experience poor adherence compared with those who received no counseling. Furthermore, those receiving intensive early adherence counseling were 59% less likely to experience virologic treatment failure. However, there was no significant difference in mortality or significant differences in CD4 counts at 18 months follow-up between those who received counseling and those who did not. There were also no significant differences in adherence, time to virologic treatment failure, mortality, or CD4 counts in patients who received alarm devices compared with those who did not.

The authors conclude: "As antiretroviral treatment clinics expand to meet an increasing demand for HIV care in sub-Saharan Africa, adherence counseling should be implemented to decrease the development of treatment failure and spread of resistant HIV."

 

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No ARVs in 'Whoonga', say Experts. 11/2/11

The drug is actually an old foe, heroin, and does not include ARVs.

11 February 2011

Johannesburg - Media in South Africa recently erupted into a frenzy of coverage of an allegedly new illegal drug, 'whoonga', said to contain life-prolonging antiretrovirals (ARVs), but experts say the drug is actually an old foe, heroin, and does not include ARVs.

The South African AIDS lobby group, the Treatment Action Campaign (TAC), has expressed concern that misreporting in the media may fuel a craze of its own and put HIV patients and ARV drug stocks in jeopardy.

Traditionally, the term 'whoonga' in South Africa referred to low grade heroin, which was often mixed with substances like rat poison and detergent to increase its volume prior to sale. Recent media reports have alleged that 'whoonga' now contains crushed ARVs and that the use of the combination of heroin and HIV treatment is widespread among the country's townships, particularly those surrounding the port city of Durban in South Africa's KwaZulu-Natal Province.

Don't believe the hype

While Anwar Jeewa, director of the Durban-based drug rehabilitation centre, Minds Alive, said a small percentage of drug users may indeed be crushing and smoking ARVs, tests conducted by the centre and by staff from South Africa's University of KwaZulu-Natal (UKZN) have found no traces of the life-saving drugs in 'whoonga' samples.

Jeewa collected and tested six 'whoonga' samples from six different Durban townships, while Thavendran Govender, with UKZN's School of Pharmacy and Pharmacology, tested a further two samples for the South African investigative TV journalism programme Carte Blanche. None of the eight samples were found to include ARVs.

Vumami Gwala, coordinator for the small, Durban-based project, Whoonga Free, says not only are there no ARVs in 'whoonga' but that most people who do crush and smoke ARVs do so because they cannot afford 'whoonga' itself.

ARV smokers themselves remain a minority of drug users, according to Jeewa, who added that those who can afford 'whoonga' may have been led to believe they were buying ARV-laced heroin by dealers or by the media's recent misreporting.

"When [addicts] buy their drugs from dealers, it's not ARVs but they are not sure themselves whether they are smoking heroin or ARVs," he told IRIN/PlusNews. "The people who are smoking ARVs are a very small minority group, I would say not more than 5 percent of drug users."

The effects of smoking ARVs remain doubtful; according to UKZN's Govender, drugs like ARVs are more easily absorbed into the body when taken orally rather than when smoked.

When taken orally, the ARV Efavirenz does have initial side-effects including dizziness, double vision and vivid dreams, effects that have fuelled abuse of the drug in pill form in prisons. But Andy Gray, a senior lecturer at UKZN's department of therapeutics and medicines management, says it is unlikely smoking the drug would produce the same effects.

"'Whoonga' is a drug problem that has already been here for years and we really need to debunk this myth that it contains ARVs," he said.

New name, same drug

According to Jeewa, 'whoonga' was previously known as "sugars" in South Africa, a name short for the internationally better-known term for low-grade heroin, "brown sugar". The drug eventually became known by the name 'whoonga', which anecdotal evidence suggests is Tanzanian; Tanzania is an entry point for heroin into Africa.

But Jeewa said making people think ARVs are a good high - coupled with a new name for "sugars" - may be all part of the game; he likened it to rebranding and repackaging a product in order to boost sales.

It is the kind of marketing ploy that feeds into the minds of addicts, according to Shamin Garda, national executive director of the South African National Council on Alcoholism and Drug Dependence.

"What happens with most addicts is that they feel the more they put into [their drugs], the better effect they have," she told IRIN/PlusNews. "If there's not even an effect [that comes with smoking ARVs], we need to educate them about the fact that it's not doing anything for them."

"The fact that they are using heroin and 'dagga' [marijuana]... those are the dependency-producing drugs and that's what we should be focusing on," she added.

With all the claims about ARVs' inclusion in 'whoonga' and not a lot of evidence to back them up, Caroline Nenguke, spokesperson for TAC, says the issue may create a dangerous situation for ARV patients and endanger drug stocks.

Incidents of ARV theft have been reported and the Department of Health has speculated that those behind some of these incidents may have intended to sell the drugs for recreational use. Nenguke says there are fears that continuing to incorrectly link ARVs to 'whoonga' could fuel more ARV thefts.

"We think that [the media] are actually driving the problem," she told IRIN/PlusNews. "The more people say 'whoonga' contains ARVs, the more drug pedlars will start trying to push it when it doesn't work at all."

 

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Novel Treatment Adopted for HIV/AIDS Drug Users. 11/2/11

Treatment stops addiction while simultaneously reducing drug cravings

Joseph Mchekadona

Tanzania yesterday became the first country in Sub Saharan Africa to roll out comprehensive treatment for Injection Drug Users (IDUs) aimed at reduction of HIV/Aids incidence and rehabilitate the addicts.

Dr Deo Mtasiwa who is the Chief Medical Officer said yesterday in Dar es Salaam that the treatment, Methadone Assisted Therapy (MAT) uses individualised dosing of medication for people who inject drugs.

“The treatment stops addiction while simultaneously reducing drug cravings; it helps people achieve stability and return to healthy and productive lives; it also reduces risky behaviour related to injection drug use and helps prevent HIV transmission while improving adherence to anti-retroviral treatment (ART), ” said Mtasiwa.

He said the project has been made possible through funding from United States (US) President’s Emergency Plan for Aids Relief (PEPFAR) and is being implemented in collaboration with the Ministry of Health and Social Welfare (MOHSW); Muhimbili University of Health and Allied Sciences (MUHAS ); the Tanzania Drug Control Programme and other local Non Governmental Organisations (NGOs).

Kinondoni district in Dar es Salaam region has been identified for the pilot project which will help to rehabilitate many drug users in the country especially those who use drugs through injections (IDUs) according to Dr Mtasiwa.

Local NGOs which will implement the programme include, Youth Volunteers Against Risky Behaviours (YOVARIBE) Centre for Human Rights Promotion TZ (CHRP –TZ), Kimara Peers and Blue Cross Society of Tanzania.

Mtasiwa said the NGOs will also offer recovery and psychosocial counseling to support adherence to Antiretroviral Treatment (ART) Tuberculosis (TB) and Sexually Transmitted Infections (STI).

He added that IDUs are vulnerable to HIV/Aids as most of them share needles and that a recent research carried out by health experts in the country found that 50 percent of women who are IDUs are HIV infected while 27 percent men who use drugs through injections are HIV positive.

Mtasiwa said community preparedness has been a top priority in MAT planning through training to conduct drug/user outreach services and for Dar es Salaam, the methadone treatment will be provided by Muhimbili National Hospital (MNH).

“Peer education and HIV prevention intervention is provided to the participating field officers and currently each officer serves 100 new injection drug users,” he said.

Dr Eva Matiko on behalf of American people said they would anticipate and try to address challenges through close and continuous follow up in phases of the planning process.

She said the experiences of MAT in Tanzania will help inform other African settings with generalised HIV epidemics in designing and providing comprehensive HIV prevention for people using drugs.

“MAT is a proven effective component of HIV prevention and Tanzania has bravely and remarkably paved way in adopting ground breaking HIV prevention for people who use drugs,” said Matiko.

Narrating how he has benefited from the therapy Mtalu Mapunda, a resident of Mwananyamala said he was happy that there is treatment for drug users in the country.

He said there are many IDU victims but they lack a place where they can get the treatment.

He said he hoped that the coming of the facility would help many ex-drug users, calling upon them to stop the practice and find other meaningful and productive things to do.

Mtalu said ending addiction to drugs is not impossible as many people think. “It’s very easy only if one is willing to stop.”

 

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Weekly Text Messages Improve HIV Drug Adherence in Kenya. 25/1/11

Text message reminders on adherence to ART among patients

AIDSMap

By Carole Leach-Lemens
25 January 2011

Weekly text message (SMS) reminders increased the proportion of patients who achieved 90% adherence to antiretrovirals by 13-16% over one year in a randomised trial in rural Kenya, Cristian Pop-Eleches and colleagues report in the advance online edition of AIDS.

Weekly reminders also reduced the frequency of treatment interruptions, strongly linked to treatment failure and the development of drug resistance. Second-line therapy in resource-poor settings is often unavailable and when it is the cost can be as much as 17 times greater than first-line, note the authors. So prevention of adherence-related treatment failure is critical.  

While antiretroviral therapy continues to reduce death and disease in people living with HIV, incomplete treatment adherence is a major factor of treatment failure, drug resistance, HIV disease progression and death.

In resource-poor settings evidence suggests adherence is as good, if not better than in resource-rich settings. However, some studies have found adherence declines over time. Reasons include: increasingly larger numbers of people are on ART in rural areas where access to continued care and support is severely limited because of a lack of financial, human and transportation resources.

Mobile phone messaging has been proposed as one way to support adherence and minimise loss to follow-up among people with HIV taking antiretroviral therapy.

The study released this week is the second randomised trial conducted in Africa to show that text message adherence alerts improve some aspect of adherence. A study also conducted in Kenya reported significantly better adherence and viral suppression in those who received weekly reminders.

The authors looked at the efficacy of text message reminders on adherence to ART among patients attending the Chulaimbo Rural Health Center (CRHC) in Nyanza Province, Kenya. CRHC, a government-run health facility, hosts an HIV clinic run by the Academic Model Providing Access to Healthcare (AMPATH) since 2005. 45% of the study participant households reported having a cell phone and 97% lived within an area of cell phone network coverage.

Beginning in June 2007 431 patients, eighteen years of age and older, who had started ART within the previous three months were enrolled and randomly assigned to a control group or one of the four intervention groups. Participants received SMS reminders in one of three languages (English, Dholuo and Kiswahili). Messages were of either short (“This is your reminder”) or long (“This is your reminder. Be strong and courageous, we care about you”) text and sent on a daily or weekly basis. Adherence was measured using the medication event monitoring system (MEMS). All participants received mobile phones to use as they wished. All participants received assistance to charge their phones and phone credit was added on a regular basis.

Overall adherence in the control group after 48 weeks was 75.8%, declining over time. 60% of the control group achieved 90% adherence within the first two weeks which declined to 46% in weeks 37-48. The authors note that 90% of the control group had at least one treatment interruption that lasted more than two days. This increased over time from 40% in weeks 1-12 to 58% in weeks 37-48 (P=0.001).

The number of participants with 90% adherence in the two groups receiving weekly reminders (short and long texts) was significantly higher than in the control group (53% compared to 40%, P=0.03). In the group receiving daily reminders attainment of 90% adherence did not differ much from the control group (41% compared to 40%, P=0.92).

In addition those receiving weekly reminders were also much less likely to have treatment interruptions for longer than 48 hours during the 48 week follow-up time (81% compared to 90%, P=0.03).

However the authors note that adding words of encouragement was no more effective than a short reminder or no reminder. They suggest that future cell phone interventions look at how message content and form affect behaviour. Shared mobile phone use and the real possibility of changing numbers also need to be considered.

Further study is needed to understand why weekly reminders were more effective in improving adherence than daily reminders, the authors note. They add that sending the reminder was not linked to the time when the MEMS bottle was opened. Technology is now available to link the two.

Limitations include the fact that no distinction could be made between improved dose-taking behaviour and improved use of the electronic medication monitor. Viral load measures were not taken so differences in adherence were not linked to viral suppression.

The authors conclude that “these results suggest that SMS reminders may be an important tool to achieve optimal treatment response in resource-limited settings.”

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Free Online Tool may Help Doctors make Treatment Decisions for HIV-positive Patients with Drug Resistance. 20/1/11

Resource can help doctors select the most effective combination of anti-HIV drugs for patients

AIDSMap

Michael Carter
20 January 2011

UK investigators have developed an online resource that can help doctors select the most effective combination of anti-HIV drugs for patients with extensive experience of antiretroviral therapy. Evaluated in two studies published in the January edition of AIDS Patient Care and STDs, suggestions made by the tool led to doctors changing their initial treatment decision in a third of cases. Physicians found the resource easy to use, and the majority said that they would consider using it in the future.

An updated version of the resource, the HIV Treatment Response Prediction System (HIV-TRePS), is now freely available on the internet, and is based on a computer model that includes information gathered from 65,000 HIV-positive patients across the world.

Doctors enter information about their patients, including resistance to HIV drugs, antiretroviral treatment history, CD4 cell count, and viral load. The programme then suggests the five combinations of drugs which are likely to be most effective.

“HIV-TRePS is an innovative and important took to improve the health of people with HIV”, said Dr Julio Montaner of the British Columbia Centre for Excellence in HIV/AIDS. His clinic was involved in the development of the resource.

There are now 25 antiretroviral drugs available and the goal of HIV therapy is an undetectable viral load. However, many patients do not achieve this outcome and selecting the best combination of drugs for patients with extensive experience of therapy anti-HIV medications, especially if they have drug resistance, can be difficult.

A group of investigators therefore came together to develop a computer model that could accurately predict responses to antiretroviral therapy. The UK-based researchers collaborated with HIV physicians in 15 different countries.

Initial analysis showed that a programme could help doctors make treatment decisions. But before making the models available the investigators wished to test their “potential utility in clinical practice.”

Two studies were designed. It was intended to recruit 150 patients to a prospective study. However, only ten individuals were recruited to the study when it was stopped early because of the introduction of three new drugs (etravirine, maraviroc and raltegravir) that provide important options for heavily treated patients.

The second study was retrospective and reviewed 104 cases.  In both studies, doctors entered into the model the genotypic resistance profiles of their patients, together with HIV treatment histories, viral load and CD4 cell count.

Doctors were also asked to input the combination of drugs they were considering for their patients.

Five treatment combinations most likely to suppress viral load were then suggested by HIV-TRePS. The 24 physicians who participated in the study then entered the therapy they actually prescribed, and results showed that in a third of cases they changed their initial treatment decision after using the programme.

In only five instances did the doctors actually use a combination suggested by the programme. In the other 33 cases, doctors amended the recommendation to take into account patient preference, their own judgment, and tolerability.

Nevertheless, after using the programme doctors were more likely to prescribe a regimen that consisted of only three drugs.

“Review of the report led to physicians to reflect on their treatment decisions and the final decision reached was improved as a result – with fewer drugs and a superior predicted response,” comment the investigators.

Physicians found the programme easy to use.  Most said it was “quite useful” (22%) or  “satisfactory” in making treatment decisions, a 30% reported they would use it “often,” and 48% “sometimes.” Only one doctor indicated that he would never use it, and this was because the individual provided care to patients whose treatment was straightforward.

“The encouraging results indicate that the system is easy to use and has potential to provide significant benefits in terms of simplicity and acceptability of therapy, the virologic response to that therapy and its costs,” conclude the researchers, who believe the results warrant "further development and clinical study."

An updated version of the system has been made available, and an experiment tool for resource limited settings tool that does not require resistance data is being developed.

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New Method to Correct Mortality Rate Biases in HIV Treatment Programs. 18/1/11

Calculator corrects mortality estimates for loss to follow-up

18 January 2011

HIV treatment programs in sub-Saharan Africa should routinely report mortality rates among patients who remain in the programs and those patients lost to follow-up, according to a study by Matthias Egger and colleagues from the International Epidemiologic Databases to Evaluate AIDS in East Africa, Western Africa, and Southern Africa that is published in this week's PLoS Medicine.

As a substantial proportion of patients in HIV treatment programs are lost to follow-up, mortality estimates for patients in these programs can be severely underestimated, so this bias needs to be taken into account when comparing the effectiveness of different programs.

The authors arrived at these conclusions by developing a nomogram (calculator) that corrects mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting antiretroviral therapy in an HIV treatment program is a weighted average of mortality among patients lost to follow-up and patients remaining in care.

In an accompanying Perspective, Gregory Bisson from the University of Pennsylvania School of Medicine (not involved in the research) comments that "currently we know little about the biology and behaviors that underlie loss to follow-up, but with 5.2 million people on [antiretroviral therapy], and more starting soon as a result of the 2010 WHO guidelines recommending HIV treatment earlier during disease progression, a greater understanding of loss to follow-up in its various forms is needed in order to keep the HIV treatment effort on track." He adds, "by addressing the effects of loss to follow-up on programmatic mortality estimates, and by providing monitoring efforts with a useful new tool, Egger and colleagues have helped address this need."

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Updates to US HIV Treatment Guidelines. 11/1/11

A number of updates to its HIV treatment guidelines for adults

AIDSMap

By Keith Alcorn
11 January 2011

The United States Department of Health and Human Services released a number of updates to its HIV treatment guidelines for adults on January 10th.

These include:

-A refinement of recommendations on when to start antiretroviral treatment in people diagnosed with tuberculosis.

In people with CD4 counts below 200 cells/mm3 antiretroviral treatment should begin no more than two to four weeks after starting TB treatment. In people with CD4 counts between 200 and 500 antiretroviral treatment should be delayed no more than two to eight weeks after starting TB treatment. A majority of the guidelines panel also recommend that HIV treatment should be commenced within eight weeks of starting TB treatment in people with CD4 counts above 500 cells/mm3.

-CD4 cell counts in people on suppressive antiretroviral therapy should only be monitored every 6 to 12 months, unless there is a concomitant clinical condition or the patient is receiving immunosuppressive drugs.

-Virological failure should be defined as a viral load above 200 copies/ml, in order to rule out isolated blips or assay varations.

-Maraviroc /AZT/3TC is added to the list of acceptable regimens for first-line treatment.

Combining maraviroc with either Truvada (Tenofovir/FTC) or Epzicom (abacavir/3TC, marketed as Kivexa outside North America) is described as `may be acceptable but more data needed`.

-Saquinavir-based treatment is downgraded from `Alternative` to `Acceptable but use with caution` as a result of a recent warning regarding abnormalities in cardiac rhythm in healthy volunteers who received the drug.

-Genotypic resistance testing for integrase inhibitor resistance should be considered at the time of failure of integrase inhibitor-containing treatment, in order to guide any future use of integrase inhibitors. At present there is only one integrase inhibitor, raltegravir, available for prescription. Subsequent viral suppression after failure of raltegravir treatment may make it difficult to determine the integrase inhibitor resistance profile, should a patient require a new integrase inhibitor in the future. The panel also encourages physicians to think about the possibility of transmitted integrase inhibitor resistance in patients new to treatment, and in particular to consider whether the patient’s source of infection was receiving an integrase inhibitor, since integrase inhibitor resistance is not currently a part of the standard panel of genotypic resistance tests that ought to be carried out for any patient starting treatment.

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Scale up of Treatment Linked to Rise in Loss to Follow-up, but Those in Care Continue to do Well. 5/01/11

Low death rates and high rates of viral load suppression have been sustained

AIDSMap

By Carole Leach-Lemens
5 January 2011

Low death rates and high rates of viral load suppression have been sustained throughout the seven years of scale-up in a community-based antiretroviral treatment service in a poor area of Cape Town, South Africa.

However, the cumulative probabilities of loss to follow-up (LTFU) and virological failure increased over time suggesting a decreased capacity to support the long-term therapy needs of a growing caseload, according to Mweete D. Nglazi and colleagues in a prospective cohort study reported in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.

Over 5 million people were estimated to be getting antiretroviral treatment in low- and middle-income countries by the end of 2009, 3 million of whom are in sub-Saharan Africa with the majority in South Africa.

Reports of the early successes of ART programmes in sub-Saharan Africa achieving good immunological, virological and clinical responses have been challenged by reports of high mortality rates and high losses to follow-up. This may be explained, in part, by patients diagnosed late and already seriously ill.

However, few studies have reported on the long-term outcomes of large cohorts in sub-Saharan Africa, in particular looking at how ever-increasing caseloads affect a programme’s ability to deliver and maintain quality of care over time.

Success of antiretroviral treatment depends on a team of health care workers and counsellors being able to meet often overlapping short- and long-term goals by delivering treatment effectively.

Critical short-term goals include rapid reduction of death rates by diagnosis and treatment of co-morbidities, provision of co-trimoxazole prophylaxis and getting the best clinical and virological responses to ART; long-term goals include keeping patients on treatment with good adherence and sustained suppression of viral load.

The authors undertook a prospective cohort study of treatment-naïve patients aged 15 years and over enrolled between September 2002 and September 2008 in a community-based antiretroviral treatment service in a poor area of Cape Town, South Africa. Follow-up data ended in September 2009.

By September 2008 3162 patients had started ART with a maximum annual enrolment of 783 patients in the 12 month period of 2005-2006. 67% were women and the median age was 34 years.

Median baseline CD4 cell counts changed significantly over successive enrolment periods from 87 cells (interquartile range (IQR): 45-145) in 2002-2004 to 121 cells (IQR:60-178) in 2007-2008. Median follow-up was 2.4 years (IQR: 1.2-3.8).

Ratios of patients to peer counsellors increased four-fold from 2002-2004 to 2007-2008; and doctor to patient ratios increased by close to 50% from 1:202 in 2002-2004 to 1:395 in 2007-2008.

After six years the cumulative probability of death and loss to follow-up was 37.4%, comparable to another programme in Cape Town.

Retention of over 60% of patients on treatment and in care after six years is a success, note the authors. However, with each successive year of enrolment the risk of being lost to the programme increased, raising concerns about the programme’s ability to maintain an acceptable standard of care.

The authors chose to look at the different losses separately as well as early and late virological responses to antiretroviral treatment to further understand this trend and how it affected quality of care.

The one year mortality rate of 7.9% in this cohort, with many at an advanced stage of illness, is very low for sub-Saharan Africa where rates vary between 8% and 26%. The authors stress that even as caseloads increased low mortality rates in the first year of treatment did not change over time.

Early viral suppression of <400 copies/mL at 16 weeks in 93% or more of patients also did not vary over time.  

Additionally the proportion of those with CD4 cell counts <200 cells/mm³, a subset recognised as having an ongoing high risk for early mortality, was looked at.  From 90% at baseline, this proportion decreased to approximately 20-30% after 48 weeks on antiretroviral treatment and did not vary significantly with successive years of starting ART.

The authors note that these results show that the initial care and treatment support in the first months on ART was maintained regardless of an increasing caseload.  

The authors note that one of the primary challenges after the first year of ART is to keep patients on treatment and in care.

While the cumulative probability of being lost to follow up after six years was 29.1% not dissimilar to another programme in Cape Town, the authors found that as elsewhere this proportion increased significantly with each successive year of enrolment.

This may be explained, the authors note, by an increasing caseload which brings with it increasing clinic waiting times, shorter consultations, reduced opportunities for counselling and adherence support as well as human resources further overstretched for patient tracing following missed appointments.

The implication that increasing clinic caseloads led to decreasing treatment support over time was supported by the rise of an increasing risk of virological failure along with the increasing rates of LTFU. 

At six years the probability of virological failure in the whole cohort was 23.1%, many of whom had drug resistant mutations. An increase in drug resistance leads to increased switching to protease-inhibitor second-line regimens. Regimens that are not only considerably more expensive but after which there are few if any other options.

The authors note that the South African population is highly mobile making long-term care especially difficult. They suggest more efficient referral and patient tracking systems are needed to provide quality uninterrupted care.

Strengths of the study include very complete data from a cohort of over 3000 with one of the longest follow-up periods in the context of a public sector ART programme in sub-Saharan Africa.

Limitations include, note the authors, an analysis of many end-points raising the possibility of false-positive findings.

They add that while increasing caseloads are suggestive of increased LTFU and virological failure over time they found no causal association.

The authors conclude that “successful early outcomes were sustained between sequential calendar years during seven years of scale-up. In contrast, the increasing cumulative probabilities of LTFU or virological failure may reflect decreasing capacity to adequately support patients during long-term therapy as clinic caseload increased.”

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Gilead Sciences Extends Study of HIV Drug. 10/01/2011

Shares of Gilead Sciences fell 17 cents to $37.33 in morning trading.

Bloomberg

Foster City, Calif. (AP) — Gilead Sciences Inc. said Monday that, at the recommendation of the Food and Drug Administration, it will double the length of its late-stage study of HIV drug candidate elvitegravir to almost two years.

Gilead said the study, which compares elvitegravir to Merck & Co.'s drug Isentress, will now last 96 weeks instead of 48 weeks. In a filing with the Securities and Exchange Commission, Gilead said the extension will allow it to collect longer-term safety and effectiveness data.

Gilead said the extension will not affect trials of its four-drug "quad" cocktail. That cocktail combines the drug candidates elvitegravir and cobicstat, along with its already-approved Truvada therapy, into a single tablet.

Shares of Gilead Sciences fell 17 cents to $37.33 in morning trading.

 

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Treatment News 2010

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Herb Halts Spread of HIV in Blood. 23/12/10

Imbasa as it is called locally in Emuhaya, or Tylosema fassoglensis botanically

PlusNews

By Gatonye Gathura
23 December 2010

Nairobi — A vine which grows wildly in western Kenya and found to have antiretroviral properties is among a handful of neglected inventions in Africa with the potential to change the continent's health landscape.

Imbasa as it is called locally in Emuhaya, or Tylosema fassoglensis botanically, also grows in parts South Nyanza and Maseno Hills.

It has been the subject of intense study by researchers from Kenyatta University, Kenya Medical Research Institute, Maseno University and North Carolina University in the US.

Using an extract from the climber, researchers led by Dr Michael B. Odotte, have developed a food supplement called Sunguprot now under commercial incubation at the Kenya Industrial Research Institute.

"It is a protein based protease inhibitor, meaning that it stops the replication of HIV in the body, and has been certified by the Kenya Bureau of Standards as fit for human consumption," said Dr Odotte.

Last week Sunguprot was part of a slew of papers published by Canada's McLaughlin-Rotman Centre for Global Health identified as having the potential to offer Africa a home grown health solution.

Sunguprot, says the paper published in the UK-based BioMed Central, is a promising product but it is being held back by lack of advanced scientific equipment to isolate compounds and funding to carry out large clinical trials.

Writing a forward for the papers that included innovations by the Kenya Medical Research Institutes and the Nairobi based International Centre for Insect Physiology and Ecology, Kenyan scholar at Harvard University Dr Calestus Juma says this has come at an opportune time.

"The publication has come at a time when firms in industrialised countries are rethinking their global strategies, especially in relation to the location of new research and production facilities. These papers show that some African countries could be viable partners as they seek to become part of the global knowledge ecology."

Sunguprot, which was featured in the Nation last year, and comes in the form of flour for porridge, is described as a herbal food supplement with both antiretroviral and nutritive properties, ideal for people suffering from HIV/Aids, the malnourished and the aged.

Talking to the Nation, Dr Odotte said safety and efficacy studies had been carried out in conjunction with the Kemri and it had been found to be safe in primates and significantly lowered the HIV in the blood.

"We were funded by the National Council for Science and Technology to carry out limited clinical trials but we would still need to carry out larger studies," Dr Odotte said.

He said, they are working with Maseno University on how to domesticate the wild plant for both commercial and conservation. "Already some farmers in Nyatike and Rongo are growing the plant on experimental bases."

The limited trials carried out under Prof John Mecham of the Department of Biology, Meredith College and Prof Michael Otieno, Department of Pre-Clinical Sciences, Kenyatta University,

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Earlier Initiation of Antiretroviral Therapy Should Be Highest Priority for Expansion of HIV Care, Study Finds. 21/12/10

This should help resource-limited nations to phase in the implementation of the new 2010 WHO recommendations for HIV treatment.

21 December 2010

Earlier initiation of antiretroviral therapy should be the highest priority for global expansion of HIV patient care. This finding, from a paper published in PLoS Medicine, should help resource-limited nations to phase in the implementation of the new 2010 WHO recommendations for HIV treatment.

"Immediate scale-up of the entire WHO guideline package may be prohibitively expensive in some settings," said lead author Rochelle P. Walensky, MD, MPH of the Massachusetts General Hospital, Boston. "In many resource-limited settings, the relevant policy question is: What to do first?"

The new WHO guidelines include three major changes: initiation of ART when CD4 levels drop below 350/µl, rather than waiting until they reach 200/µl; replacing the antiretroviral drug stavudine with the less-toxic but more expensive tenofovir for first-line treatment, and switching patients to second-line ART regimens when the first-line regimen fails.

Findings from Walensky and colleagues demonstrate that earlier ART initiation increased 5-year survival from 80 to 87% and showed substantially improved early clinical outcomes compared to either using tenofovir for first-line treatment or providing second-line regimens. In settings where ART initiation at 350/μl is already available, switching stavudine to tenofovir offers clinical benefit and is less costly than adding second-line regimens. Finally, the authors demonstrate that the availability of second-line regimens offers major survival benefits (greater than 4 years per person) but at substantial increases in cost.

The authors conclude: "The entire package of recommendations proposed by the WHO is cost-effective in South Africa (incremental cost-effectiveness ratio of US$2,370 per year of life saved). However, in settings where immediate implementation of all of the new WHO treatment guidelines is not currently feasible, antiretroviral treatment initiation at CD4 < 350/µl provides the greatest short- and long-term survival advantage and is highly cost-effective."

Rochelle Walensky is an Associate Professor of Medicine at Harvard Medical School. Additional co-authors of the PLoS Medicine report are Andrea L. Ciaranello MD, MPH, Sarah B. Lorenzana, Adam W. Stoler and Kenneth A. Freedberg, MD, MSc, MGH Department of Medicine; Robin Wood, FCP, MMed, DTM&H, Desmond Tutu HIV Centre, University of Cape Town; A. David Paltiel, PhD, Yale School of Medicine; and Xavier Anglaret, MD, PhD, INSERM Unité 897, Centre de Recherche "Epidémiologie et Biostatistique." The study was supported by grants from the NIAID, NIDA, and the Doris Duke Charitable Foundation.

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Once-daily Darunavir Approved for some Treatment-experienced Patients in US. 14/12/10

They do not have darunavir-associated resistance mutations.

AIDSMap

By Keith Alcorn
14 December 2010

The United States Food and Drug Administration has approved new dosing for the protease inhibitor darunavir (Prezista) that will allow the drug to be dosed once daily for patients with prior treatment experience, provided they do not have darunavir-associated resistance mutations.

The recommended oral dose for treatment-experienced adult patients with no darunavir resistance associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V) is 800 mg Prezista once daily with ritonavir 100 mg once daily and with food.

The recommended oral dose for treatment-experienced adult patients with at least one darunavir resistance associated substitution (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V) is 600 mg Prezista twice daily taken with ritonavir 100 mg twice daily and with food.

For antiretroviral treatment experienced patients genotypic testing is recommended. However, when genotypic testing is not feasible, Prezista/ritonavir 600/100 mg twice daily dosing is recommended.

The decision to authorise once-daily dosing for treatment-experienced patients is based on the findings of the ODIN trial, which compared once and twice-daily dosing of darunavir/ritonavir in treatment-experienced patients without darunavir resistance.

Prezista is already approved for once-daily dosing for patients new to HIV treatment in both the United States and the European Union.

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Tenofovir with 3TC or FTC Associated with Lower Lipid Increases than other NRTI Pairs. 14/12/10

Comparisons of dyslipidemia and cardiovascular disease risk factors associated with antiretroviral medications should focus on individual agents rather than on class effect

AIDSMap

By Michael Carter
14 December 2010

The combination of tenofovir and 3TC (or FTC) is associated with smaller increases in lipid levels than other pairs of NRTIs in patients starting HIV treatment for the first time, US researchers report in the online edition of AIDS.

Although tenofovir (Viread) with 3TC (lamivudine, Epivir) or FTC (emtricitabine, Emtriva) was associated with better total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels, it did not have a beneficial effect on high-density lipoprotein (HDL) cholesterol.

“Findings from this study demonstrate that comparisons of dyslipidemia and cardiovascular disease risk factors associated with antiretroviral medications should focus on individual agents rather than on class effect,” comment the investigators.

Cardiovascular disease is now an important cause of death in patients with HIV. The exact causes are unclear, but increases in lipid levels have been seen in patients after they start antiretroviral therapy.

Most of the research investigating the association between antiretrovirals and abnormal lipid levels has focused on the impact of the drug classes. Little attention has been paid to the effect of individual agents.

The majority HIV treatment combinations include a pair of drugs from the nucleoside reverse transcriptase inhibitor (NRTI) class of antiretrovirals. Investigators from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort monitored changes in the lipids of 2267 patients who started potent combination HIV therapy for the first time between 1995 and 2008. After controlling for the use of drugs from other antiretroviral classes, as well as demographic , behavioural and life-style characteristics, the impact of pairs of NRTIs on changes in lipids was compared.

Mean age for the patients was 38 years, 75% were men, 55% were African American, and 21% were co-infected with hepatitis C virus.

At the time potent HIV therapy was started, the patients had a mean CD4 cell count of 173 cells/mm3 and 54% had a peak viral load over 100,000 copies/ml.

The most popular NRTI pair was AZT (zidovudine, Retrovir)/3TC (40%). The next most common NRTI pair was tenofovir/3TC (26%), followed by d4T (stavudine, Zerit)/3TC (16%). Between 2% - 5% of patients took other combinations of NRTIs. A weakness of this study is the lack of patients taking abacavir/3TC, now the most commonly prescribed alternative nucleoside pair to tenofovir/FTC.

Lipid levels increased after HIV therapy was started. The most rapid increase was observed in the first two months of treatment.

Patients taking tenofovir combined with 3TC or FTC had lower lipid levels than patients treated with other NRTI pairs.

Total cholesterol levels were significantly higher (between 10 – 22mg/dl, p < 0.001 – 0.002) among patients receiving any other NRTI combination when compared with tenofovir and 3TC or FTC.

LDL cholesterol levels  were also higher for patients taking combinations other than tenofovir/3TC or FTC, and were significantly so for those treated with ddI (didadosine, Videx)/3TC (p = 0.03).

In addition, mean triglyceride levels were lower for patients taking tenofovir/3TC or tenofovir FTC.

However, therapy with tenofovir and FTC or 3TC did not have a beneficial impact on HDL cholesterol, so called “good” cholesterol. Indeed, patients taking any other pair of NRTIs had significantly higher HDL cholesterol than those taking tenofovir and FTC or 3TC (+ 3 – 11 mg/dl, p < 0.01 – 0.02).

Improvements in health appeared to be associated with lipid increases. Each 10 cells/mm3 increase in CD4 cell count was associated with significant increases in total cholesterol, LDL cholesterol, non-HDL cholesterol and triglycerides (p = 0.008 – 0.05).

In addition each kg/m2 increase in body mass index (BMI) was associated with significant increases in total cholesterol (p = 0.02), LDL cholesterol (p = 0.006), triglycerides (p = 0.03), and non-HDL cholesterol (p = 0.009).

Smaller lipid increases were seen in patients co-infected with hepatitis C. But the investigators do not believe that this conferred any health benefits. They note, “despite having more favourable pro-atherogenic lipid profiles, HCV co-infected patients were recently shown to have higher rates of cardiovascular events among a study of US veterans.”

The investigators conclude that the study “provides additional evidence that the metabolic impact of most antiretroviral agents, particularly those used more commonly in initial regimens in the current ART era, are relatively modest.”

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Still an Uphill Battle against HIV. 7/12/10

More than one million people in the country are now receiving antiretroviral therapy

Mail & Guardian

By Rachel Cohen
7 December 2010

More than one million people in the country are now receiving antiretroviral therapy (ART) for the treatment of HIV/Aids. But South Africa still faces an uphill battle to keep up with the epidemic -- much less turn the tide.

Médecins Sans Frontières (MSF) has been working with the government and local partners in Khayelitsha and Lusikisiki in the past 10 years to provide comprehensive, integrated HIV/TB care, including ART, and we are keenly aware of the immense challenges confronting the country.

A recent report titled: "The Long Run Costs and Financing of HIV/Aids in South Africa", lays out the stark policy choices government must make today to reduce Aids deaths and avert millions of infections in the next 20 years.

The celebrated about-turn in the government's Aids policy has lead to substantial increases in government funding for HIV/Aids -- including R8,4-billion in the next three years -- and the adoption of critical policy changes, including a drive to provide ART in every primary healthcare clinic and allow nurses to initiate treatment before their patients develop life-threatening HIV-related illnesses.

These should enable wider access to treatment, prevention and testing services. But government can and must do much more to turn these commitments into reality.

First, it should immediately adopt treatment guidelines that allow earlier initiation of ART for all people with CD4 counts of less than 350 cells/mm3 as per new World Health Organisation (WHO) guidelines.

The advantages of doing so have been widely reported in scientific literature. From our own experience in neighbouring Lesotho, where the government adopted these guidelines in 2008, we know the benefits have been dramatic.

Treatment

In a two-year study we found that patients who started treatment earlier (at CD4 counts of less than 350 cells/mm3) were 68% less likely to die, 63% less likely to be hospitalised, 27% less likely to get new opportunistic infections such as tuberculosis and 39% more likely to remain in care compared with those who started when the disease was already advanced (CD4 counts of less than 200 cells/mm3). But, so far, South Africa has opted for only partial implementation of these guidelines due to resource constraints, even though the short-term cost increase could easily be offset.

Second, the welcome new national policy permitting nurses to initiate ART and allowing for task-shifting of non-clinical tasks to lay health workers needs to be transformed from policy to practice.

Our experience in Lesotho and other neighbouring countries has shown that nurse-driven HIV and TB services at the primary care level allows more people to access treatment, while maintaining good clinical outcomes for patients. Yet not one nurse in Khayelitsha, and only very few in the Western Cape and other provinces, has been authorised to initiate ART a year after the new policy was announced.

Third, South Africa should negotiate far better prices for its antiretrovirals. In spite of the fact that it has the largest number of people on ARVs in the world, it still pays significantly more for them than neighbouring countries where MSF is working, because these countries make use of the best international prices for quality generic ARVs, including fixed-dose combinations that need to be taken only once a day.

We need a tender system that will enable South Africa to access these prices and ensure that money now spent needlessly on expensive drugs can be stretched to reach more ­people who need treatment.

Researchers from the Health Economics and Epidemiology Research Unit at the University of Witwatersrand have shown that if new drug purchasing mechanisms are utilised and task-shifting is implemented, the full WHO guidelines will actually cost less than the old guidelines.

There is no reason for delay. These steps will go a long way towards increasing access to treatment. But science is now showing that we have a unique opportunity to make the quantum leap necessary to "bend the epidemiological curves", with even more ambitious new strategies.

'Treatment as prevention'

Pilot programmes to explore the feasibility and acceptability of "treatment as prevention" need to be considered with other prevention interventions, since ARVs are increasingly understood to have a major impact on reducing HIV transmission in addition to reducing HIV and TB-related illness and death.

This will require radical, out-of-the-box thinking about community-based, out-of-facility approaches to testing, drug distribution and adherence support. Economists are telling us these sorts of approaches could even be cost-saving in the long run.

And new "game-changing" technologies, which could help to ease the burden on patients, reduce the requirements of the health system and decrease the cost per patient per year, must be developed and implemented rapidly once they are validated.

These include new ARV drug delivery platforms and slower-releasing drugs, new molecular diagnostic technologies which will help to detect forms of TB that are otherwise difficult to diagnose in HIV-positive individuals, point-of-care CD4 and viral load tests and, following the promising results of the iPrEX trial, pre-exposure prophylaxis (PrEP).

After a decade of disastrous Aids denialism, the South African government is finally claiming back the leadership role everyone expected it to play in the fight against HIV/Aids. But it cannot do it alone. In addition to spending domestic funds more wisely, averting disaster will require greatly increased international financing at a time when the Global Fund to Fight Aids, Tuberculosis and Malaria is facing a budget shortfall and the United States government has ­virtually frozen Aids funding.

South Africa can and must step forward once again to lead the way in throwing off the mantle of cynicism and Aids fatigue that has set in rich countries and show that it is still possible to break the back of this epidemic.

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Switching rom Efavirenz to Etravirine Improves Mood and Sleep. 7/12/10

Patients who were currently taking efavirenz did not prefer etravirine therapy.

AIDSMap

By Michael Carter
7 December 2010

Switching from efavirenz to etravirine is associated with significant improvements in central nervous system side-effects, UK investigators report in the online edition of AIDS.

Patients were less likely to report insomnia, bad dreams and nervousness after changing treatment.

“The study demonstrates an improvement in several measures of CNS [central nervous system] toxicity when switching from efavirenz to etravirine,” comment the researchers.

However, separate research reported here on aidsmap.com found that patients who were currently taking efavirenz did not prefer etravirine therapy.

Efavirenz (Sustiva, also in the combination pill Atripla) is a non-nucleoside reverse transcriptase inhibitor (NNRT) and is recommended for use in first-line antiretroviral therapy. Central nervous system side-effects are common in patients who are taking efavirenz. They often fade within a month, but persist in a minority of patients and some individuals stop taking the drug because of them.

A second-generation NNRTI is etravirine (Intelence) and there is no evidence that it causes central nervous system side-effects. It also has a high barrier to resistance, and research suggests that it can be taken once daily.

Investigators at four large London HIV treatment centres wished to see if switching from efavirenz to etravirine was associated with an improvement in central nervous system side-effects.

They therefore designed a double-blind, placebo-controlled study involving 38 men who were taking stable antiretroviral therapy that included efavirenz.

The patients were randomised into one of two arms. One group of patients switched therapy immediately and took a combination of drugs that comprised two nucleoside reverse transcriptase inhibitors (NRTIs) plus etravirine and an efavirenz placebo. Individuals in the other arm received a combination of two NRTIs, efavirenz and an etravirine placebo.

After twelve weeks the study was unblinded and all the patients were treated with etravirine.

The study’s primary endpoint was the proportion of patients who had central nervous system side-effects at week twelve.

All the patients had been taking efavirenz-based antiretroviral therapy for at least twelve weeks and had a viral load below 50 copies/ml. Their median CD4 cell count was 510 cells/mm3.

At baseline, 90% of patients in the immediate-switch arm and 89% of those who were randomised to change treatment later had at least one moderate-to-severe central nervous system side-effects.

After twelve weeks, only 60% of those who had changed to etravirine reported such side-effects. This was a significant reduction (p = 0.041).  The proportion of patients reporting central nervous system side-effects in the delayed-change arm remained unchanged.

However, improvements in central nervous side-effects were seen in individuals in the delayed-switch arm once they changed treatment to etravirine.

After twelve weeks of therapy with etravirine, there were significant reductions in the proportion of patients reporting any moderate-to-severe central nervous system side-effect (89% to 60%, p = 0.0009), insomnia (63% to 37%, p = 0.016), abnormal dreams (57% to 20%, p = 0.001), and nervousness (29% to 9%, p = 0.046).

The mean number of central nervous system side-effects fell after therapy was switched (3 to 1, p < 0.001).

Viral load remained fully suppressed in all the patients. CD4 cell counts increased significantly after treatment was switched to etravirine (twelve week increase = 43 cells/mm3, p = 0.027).

Lipid profiles also improved after treatment was changed. There were significant reductions in both total and LDL-cholesterol (both p < 0.001).

“The advent of newer, once-daily agents should encourage active questioning about central nervous system toxicity in patients on efavirenz,” according to the investigators,  who add, “proactive switch from efavirenz may yield significant reductions in central nervous system toxicity.”

They conclude, “once-daily etravirine offers an efficacious, tolerable and lipid-friendly alternative to efavirenz in patients with persistent central nervous system toxicity.”

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Pregnancy Outcomes Similar for Efavirenz and Nevirapine in Cote d'Ivoire Women. 6/12/10

Women taking efavirenz were more likely than those treated with nevirapine to have their pregnancy terminated.

AIDSMap

By Michael Carter
6 December 2010

Pregnancy outcomes are similar for women treated with efavirenz and nevirapine during the first trimester, investigators from Cote d'Ivoire report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

No birth abnormalities were observed in children exposed to either drug. However, women taking efavirenz were more likely than those treated with nevirapine to have their pregnancy terminated.

“Our study…is the single largest study to date evaluating HIV-infected women exposed to efavirenz during the first trimester of pregnancy,” write the authors, “no increased risk of pregnancy outcomes was reported following efavirenz exposure compared to nevirapine exposure during the first trimester.”

Non-nucleoside-reverse transcriptase inhibitors (NNRTIs) are recommended for first-line HIV treatment in resource-limited settings. Efavirenz is the preferred drug because it has fewer side-effects than nevirapine.

There have been case reports of birth abnormalities in infants exposed to efavirenz in the first trimester of pregnancy. Although WHO guidelines state that women should avoid taking the drug at this time, large studies have shown that therapy with efavirenz early in pregnancy does not increase the risk of birth abnormalities.

Little is known about the comparative impact of efavirenz and nevirapine on other birth outcomes, such as stillbirth, prematurity, and low birth weight.

Therefore investigators from Cote d'Ivoire undertook a retrospective study including 344 women who became pregnant when taking either of these drugs between 2003 and 2009.

These women had a median age of 29, and their median CD4 cell count at the time they started antiretroviral therapy was 217 cells/mm3.

Most of the women (213) were taking efavirenz at the time they conceived, and the majority (190, 89%) of those taking efavirenz changed treatment(165 to nevirapine, the others to a protease inhibitor). The median duration of follow-up for women taking efavirenz was 52 days, significantly shorter than the 264 days for those treated with nevirapine.

Pregnancy outcomes were known for 326 women. Overall, 12% had a termination, 5% miscarried, and 7% had a stillbirth. Women taking efavirenz were significantly more likely than those treated with nevirapine to have a termination (14% vs. 7%, p = 0.05).

“This high frequency of abortion after early efavirenz exposure could be related to the fear of warning given by clinicians about the potential risk of congenital abnormalities,” suggest the authors.

There were 249 live births, and 11% of infants were born prematurely. The rate of pre-term delivery did not differ significantly between efavirenz and nevirapine (10% vs. 13%).

Overall, 20% of infants had a low birth weight, and comparable rates of this outcome were seen in the women exposed to either drug (efavirenz, 17% vs. nevirapine, 24%). 

No infant had a birth abnormality. The investigators believe that their study adds to the growing body of literature showing the safety of efavirenz during pregnancy.

They conclude that the results of their study are “reassuring,” but they call for “more collaborative studies and pharmacovigilence systems capturing routine data…to improve the evidence informing public health guidelines.”

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HIV Reservoir in the Brain Doesn’t Respond to Treatment Intensification. 3/12/10

Brain does serve as a protected reservoir of HIV infected cells

3 December 2010

Adding a new antiretroviral (ARV) drug with the ability to penetrate into the brain to an existing regimen doesn’t reduce residual HIV in the brain or brain inflammation in people who have good suppression of HIV elsewhere in the body, according to a study published in the December 15 issue of the Journal of Acquired Immune Deficiency Syndromes. These data suggest that the brain does serve as a protected reservoir of HIV infected cells, and that simply adding ARVs that penetrate into the central nervous system (CNS) may not shut down residual virus or reduce brain cell inflammation.

In 1996, researchers dramatically pronounced that they believed they could eradicate HIV in a person’s body within two to three years with combination ARV therapy including protease inhibitors (PIs). That same year, the first batch of PIs was approved.

Within a few years, however, this optimistic eradication hypothesis was laid to rest because researchers discovered that reservoirs of virus go unscathed by ARV therapy. And in recent years, these reservoirs have been tied to ongoing cellular inflammation, responsible for all kinds of harmful effects, including cardiovascular disease, cognitive problems and certain cancers.

This has led to the question of whether the virus is actively replicating within the reservoir or if the cells are simply releasing virus that is trapped within the cells. Answering this question is important. If ongoing replication is occurring, then simply adding more potent drugs could shut it down. If there is no active replication, and infected cells are simply releasing intact virus, then the only way to get rid of it will be to purge these infected cells entirely.

One of the suspected reservoirs is the CNS, where virus has been found despite undetectable levels in the blood. To better understand what is happening in the brain, Aylin Yilmaz, MD, PhD, from the University of Gothenburg in Sweden, and his colleagues tested the strategy of treatment intensification in 20 people living with HIV who had undetectable levels of HIV in the blood, but detectable levels in their brains.

The study involved adding one of two types of intensified ARV drugs for six weeks, and then switching over to the other type for an additional six weeks. One type of ARV, Fuzeon (enfuvirtide), doesn’t penetrate well into the brain. It’s chemical structure is too large. The other type of ARV—in this case either Selzentry (maraviroc) or Kaletra (lopinavir plus ritonavir)—does penetrate well into the brain.

The research team’s theory was that if active replication were occurring in the brain, then intensifying treatment would shut it down. If intensification didn’t work, then the experiment would prove that active reproduction was not the cause of residual virus.

Yilmaz’s team found that the latter was true. Intensifying treatment did not reduce the level of HIV present in the brain, nor did it reduce the level of cellular inflammation. The use of a drug for six weeks that did not cross over into the brain was necessary to ensure that whatever effect they found was not a result of virus reduction in other parts of the body, but what was actually occurring only in the CNS.

The authors argue that their results have two implications. First, the data indicate that the tiny bit of detectable HIV in the brain is not due to active reproduction, and that new strategies will be needed to get rid of it. Further, the data suggest that a trend toward seeking and using ARV regimens with good brain penetration might not have the intended effect of lowering HIV and reducing cellular inflammation there.

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How to make Broad ARV Access Work. 2/12/10

Zambia closer to achieving universal access to ARV's than many of its equally resource-limited neighbours.

2 December 2010

Johannesburg - Zambia is a poor country with a severe shortage of health workers, but it is closer to achieving universal access to antiretroviral treatment by the end of 2010 than many of its equally resource-limited neighbours.

Crispin Moyo of the ministry of health said about 78 percent of Zambians eligible for antiretroviral (ARV) drugs were receiving them by mid-2010 - just 2 percent shy of the universal access target of 80 percent ARV coverage.

Eligibility for treatment in Zambia depends on having a CD4 count (which measures immune system strength) of 200 or less. The country plans to adopt the latest World Health Organization (WHO) guidelines - which recommend starting patients on ARVs at a higher CD4 count of 350 or less - in 2011.

In terms of the new WHO guidelines, Zambia reached 64 percent treatment coverage by the end of 2009, ranking it fourth on the continent for ARV access after Rwanda, Botswana and Namibia, according to UNAIDS

The scale-up of ARV provision has been one of the fastest in Africa, according to the Global Health Workforce Alliance, an international consortium of governments, civil society organizations and UN agencies. From a starting point of just two clinics distributing free ARVs in 2004, there are now about 420 health facilities providing treatment, said Michael Gboun, a monitoring and evaluation (M&E) advisor at UNAIDS in Zambia.

IRIN/PlusNews spoke to Izukanji Sikazwe, a consultant to the national ARV programme, about Zambia's formula for success.

1. Task shifting

"The big chunk of our success has been due to community involvement - with the health worker shortage, there have been deliberate policies to involve the community. We have an innovative training strategy that trains lay people in the management of chronic care, which for us is really HIV.

"Maybe someone who has a grade 7 or 10 education - really basic - is able to help a healthcare provider by filling out patient forms; drawing a map of where a patient lives for follow-up; identifying who their family support is. [They do] basic triage like taking weight, height and temperature, and moving patients through the clinic from, for instance, the adherence clinic to the pharmacy.

“To deal with the shortage of pharmacists, lay people have been trained to do adherence support, so they count pills and know which questions to ask to get a sense of how the patient is doing with medication.

"Not having any incentive like a pay check or a lunch allowance has cut down our volunteer numbers. The volunteer concept is somewhat foreign in Zambia because everyone's time is spent looking for money to put food on the table ... but most do it because they've seen how persons in their families have been affected by HIV, so they are trying to get as many people on treatment."

2. External funding

"Strong partnerships and a strong will among partners to commit to funding the programme have been key - the Zambian government contributes only about 7 percent of the cost of the drugs we need. There's still a large funding gap, and a lot that needs to be done as we strive to reduce new infections ... [but] donor aid and resources have been fundamental."

3. Where there's political will, there's a way

"The government, through the President, the cabinet and parliament, took HIV seriously. In the early 2000s they moved from having a high-level cabinet committee to having a parliamentary committee on HIV ... and establishing a national AIDS council in 2002 through an act of parliament.

"They pulled resources from government and [donors like] the Global Fund [to Fight AIDS, Tuberculosis and Malaria] to map out the epidemic, and made a policy in 2004 to provide ARVs for free. The disease was at its peak, there was a funeral almost every day and almost every family had been affected - they responded to the need."

4. One funding pool, one programme, one voice

"We have one national programme. Training on any treatment guidelines was all standardized … partners bought into that and worked within that national framework. [Implementation] wasn't fragmented ... and the messages we were sending were the same.

"We have one national M&E system, where all partners involved in HIV care and treatment channel data. [In 2006] we introduced the smart care card - electronic-based [patient record] system - and patients can move with that card anywhere. That is part of any ARV site's M&E, which collects the same clinical information.

"We have one national logistic pipeline system for procuring ARVs and other HIV-related commodities. All partners are putting funds into one basket, and goods are procured from this one basket. One system at a national level lets you know exactly how much of something you have, where it is, and where it's needed."

5. Ready-to-go ARV sites

"Some of our ARV sites are supported by partners that are mostly US-funded. They're able to work with clinic staff to get them ready for the inspections needed to be accredited for ARV provision. They spend months on the ground working on patient flows, basic ARV requirements, training, and standard operating issues. When inspectors visit clinics, everything is ready to go and has been operating like that for months."

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World AIDS Day: 1 Million Now on HIV Meds in South Africa. 1/12/10

Out of a population of 50 million, 5.6 million are living with HIV.

1 December 2010

One million people are now on antiretroviral (ARV) treatment in South Africa, according to an announcement December 1 by South African Deputy President Kgalema Motlanthe, which was reported by Agence France-Presse.

South Africa has one of the highest rates of HIV infection in the world. The United Nations estimates that out of a population of 50 million, 5.6 million are living with HIV. The country went through nearly a decade of inaction on the epidemic—largely a result of then President Thabo Mbeki’s skepticism about the link between HIV and AIDS. This changed toward the end of the past decade, with the implementation of one of the largest ARV distribution programs in the world.

Deputy President Motlanthe and Health Minister Aaron Motsoaledi kicked off their World AIDS Day observation by visiting the homes of households affected by the epidemic in a rural South African village. “What we are observing here is the devastation of HIV/AIDS. All four houses we visited here were headed by grandmothers who are looking after orphans,” said Motsoaledi, adding: “What is left for us is to see how we pick up the pieces.”

Picking up the pieces is something that the country has been quick to do in recent years. The country now has the highest rate of people with HIV on ARV therapy on the African continent, and in the past year it hit this new milestone.

“More than 200,000 new patients have been initiated on ARVs since April this year, bringing a total number to 1 million,” Motlanthe told a public gathering to mark World AIDS Day in the eastern province of Mpumalanga.

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TAC: The Next Step. 1/12/10

Dubula believes the next challenge is resources, human and financial.

Treatment Action Campaign

By Lungi Langa
1 December 2010

Almost ten years ago a 22-year-old woman was told that she was HIV-positive, news that would change her life forever. Today, she runs one of the most successful civil society activist groups, widely credited for many advances in the lives of people living with HIV.

Vuyiseka Dubula is no shrinking violet.

She’s not someone who easily jumps on a soapbox and rattles off a number of statements. But when she speaks, people tend to listen, even if it was a bit of battle to get them do so at first.

“Some relationships were odd at the starts. Some of the political and union leaders, and even donors, saw us as children. I soon realised I needed to speak with authority and present myself as a leader. I knew I couldn’t change them, but I could package my message in a different way,” says Dubula, sitting in the Treatment Action Campaign Cape Town office.

Without hesitating for a second when recalling dates or places or details, the TAC’s General Secretary shares how she came to find herself in her current position.

Diagnosed at a clinic in Green Point at 22, Dubula headed for Khayelitsha after a nurse told her she had “heard a rumour they had treatment”.

“When I got there it was the MSF (Medecins Sans Frontieres) clinic, a two roomed bungalow at the time,” she recalls.

It took the young woman two months to “work through” her diagnosis and she credits her fellow TAC activists with carrying her through tough times. “I saw young people who were not drowning in misery, but people who had empowered themselves, I wanted to know more,” she recalls.

Dubula was soon starting a TAC branch in her Phillipi backyard. It grew from five people to a fully-fledged community branch.

Dubula worked her way through various levels at TAC, but always remained involved in treatment literacy. “My passion has always been treatment literacy, maybe it was my comfort zone,” she smiles.

Seven years after joining the TAC Dubula was elected to the General Secretary job, a position she was elected to again at the group’s recent Congress in Johannesburg.

“It’s a challenging position, for me a young person and as a woman,” says Dubula, who has been instrumental in establishing a leadership programme within TAC.

She also believes that TAC must be led by a collective leadership where they learn from each other and manage the challenges together.

“I feel very proud that we are able to set the foundation for the next generation of leaders,” she adds.

Dubula describes health minister Dr Aaron Motsoaledi as “very inspirational”.

“He faces very serious challenges, especially at provincial level and the challenge for us as the TAC is how we help and support without being co-opted into government,” she says.

Looking back, she remembers being “very motivated” during the reign of former health minister Dr Manto Tshabalala-Msimang and President Thabo Mbeki.

“I never felt we weren’t going to win, they motivated us to do so much, but seeing friends and relatives die during this time, evoked a deep anger in us.

“I think what also helped at the time was that we knew our voices were being heard beyond our borders, the international community really supported us.

“But seeing people you work with so closely every day die, it confronts you with the fact that you could also die and it made me feel angry and powerless. These were some of my lowest moments,” says Dubula. “I knew if we did not accelerate our efforts I would be next. I understood that we should be seeing people dying of a accidents, not of a manageable, chronic disease.”

Dubula believes the next challenge is resources, human and financial.

“We need billions. Government has the tools and information, but we need to think about how we all mobilise the resources we have,” she says.

Resolutions took by the TAC at its recent Congress covered a range of issues.

Under prevention, treatment, care and support, the TAC committed to intensifying its work in supporting the implementation of the National Strategic Plan (NSP), with an emphasis on Prevention of Mother to Child transmission, male circumcision, the TB and HIV link and scaling up of treatment.

Within gender-based violence, the meeting resolved to redouble efforts to combat gender- based violence through community-based work and advocacy, to formalise its work with men and to strengthen its lesbian, gay, bisexual, transgender and intersex sector.

Focusing on the national, provincial and district AIDS councils, the Congress examined ways of mobilising parties such as traditional healers, labourers and leaders to participate effectively in these bodies. It resolved to use local governments as platforms to push for greater commitment from local politicians to the NSP. The Congress also committed to lead the process of formulating a new NSP to follow on the current one.

On strengthening the health system, the National Health Insurance featured prominently, with TAC committing to a high level of engagement with the planning process “such that concerns regarding funding, management issues, capacity and possible inappropriate private sector user charges (fees) could be addressed”.

The congress also committed to resolve shortages in health sector workers by calling for the re-opening of colleges and incorporating community health care workers into the system.

The support activist organisations in Zimbabwe and Swaziland would continue as well as the sharing of treatment literacy expertise across the continent and lobbying globally for political will and commitment of resources to address HIV/AIDS challenges.

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ARVs also Fight HIV Infection. 24/11/10

Some protection against HIV infection in HIV-negative people

24 November 2010

An antiretroviral drug currently used to treat people with HIV has now been found to offer some protection against HIV infection in HIV-negative people. A new study has revealed that taking the ARV, Truvada, once a day reduces the risk of HIV infection by nearly 44% in gay men.

"In a finding with the potential to fundamentally change strategies to slow the global HIV epidemic, a new study called iPrEx shows that individuals at high risk of HIV infection who took a single tablet containing two widely used HIV medications, emtricitabine and tenofir (FTC/TDF also called Truvada), experienced an average of 43.8% fewer HIV infections that those who received a placebo pill," reads a statement by the research group responsible for the study, Prexposure Prophylaxis Initiative. The study was reported in the New England Journal of Medicine.

Truvada yielded "positive results" when administered to 2,499 gay men and transgendered women between the ages of 18 and 67, the Medical Research Council said in a statement. Half of the men took Truvada, while the other half took a placebo. In all, 64 HIV infections were recorded among the group who received a placebo pill, while 36 HIV infections were recorded in the group taking the study drug.

The results were the first showing that oral use of anti-retroviral drug among HIV negative gay men could provide protection from the virus.

SA component of the trial

The Desmond Tutu HIV Foundation, based at the University of Cape Town Health Science Faculty, was selected as one of 11 international sites to participate in this groundbreaking HIV prevention trial. The trial study was conducted in South Africa, Brazil, Ecuador, Peru, Thailand and the United States between July 2007 and December 2009.

The Medical Research Council's Gita Ramjee said the results gave hope for the successful use of new biomedical technologies, together with current options such as condoms and male circumcision, for HIV prevention.

Good year

"This has been a good year in terms of HIV preventions," said Prof Linda-Gail Bekker from the Desmond Tutu HIV Foundation at the launch of the results. Apart from the positive results achieved in this study, in July 2010, a study known as CAPRISA 004 found evidence that a topical gel containing 1% tenovofir helped reduce HIV negative women's risk of HIV infection via vaginal sex.

However, the antiretroviral pill is available by prescription in many countries right now, while the microbicide gel is made only in small amounts for clinical trials. Putting the power to protect themselves in the hands of patients and their clinicians.

The protection, known as “pre-exposure prophylaxis” or “PreP,” is also the first new form available to men, especially men who cannot use condoms because they sell sex, are in danger of prison rape, are under pressure from partners or lose their inhibitions when drunk or high.

Further results

The iPrEx study found that the prophylaxis was more protective among those who reported taking the pill more regularly. Among participants who used the tablet on 50% or more of days, risk of HIV infection fell by 50.2%; among those who used the pill on 90% or more of days, it reduced infection risk by 72.8%.

No serious side effects to the drugs were reported in the trial. Side effects included a small number of reports of low-grade transient nausea, which dissipated after several weeks - such symptoms are relatively common after initiation antiretroviral therapy. In addition, isolated mild elevations of creatinine, a naturally occurring molecule filtered by the kidneys, occurring in a small number of individuals receiving the active drug, resolved spontaneously or with discontinuation of the pill. Slight increases were also detected in headache and unintentional weight loss among participants in the study arm that received FTC/TDF.

More about the trial

In addition to the medication (Truvada or the placebo), all study participants received a comprehensive package of prevention services designed to reduce their risk of HIV infection throughout the trial, including HIV testing, intensive safer sex counselling, condoms and treatment and care for sexually transmitted infections.

"iPrEx proves that PrEP provides important additional protection against HIV when offered with other prevention methods such as HIV testing, counselling, condom use and management of sexually transmitted infections," said iPrEx Protocol Chair Robert Grant, MD, MPH of the Gladstone Institutes and the University of California and San Francisco. "As with other prevention methods, the greatest protection comes with consistent use. I hope this finding inspires a renewed commitment from communities, industry, and government to stop the spread of HIV."

The iPrEx study is a double-blind, placebo controlled Phase III clinical trial that began in 2007. It is the first human efficacy study of PrEP to report data.

Ongoing research

Meanwhile, the HIV Prevention Research Unit was undertaking another trial called Vaginal and Oral Intervention to Control the Epidemic.

The study is conducted among HIV negative women among several communities in Durban, with results expected in 2013. -(Wilma Stassen/Health24/Sapa, November 2010)

 

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For HIV-Positive Patients, Delayed Treatment a Costly Decision. 24/11/10

Require tens of thousands of dollars more in care over the first several years of their treatment.

24 November 2010

HIV infected patients whose treatment is delayed not only become sicker than those treated earlier, but also require tens of thousands of dollars more in care over the first several years of their treatment.

"We know that it's important clinically to get people into care early because they will stay healthier and do better over the long run," says Kelly Gebo, M.D., M.P.H., an associate professor of medicine in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine and the study's senior author. "But now we know it's also more costly to the health care system for potentially decades and a serious drain on our limited health care dollars."

Gebo says her team's findings highlight the importance of motivating people who are at risk to seek HIV testing and of reducing the time between the first positive HIV test and the first visit to an HIV clinic for care.

Patients with HIV are living longer and healthier lives, thanks to advances in antiretroviral therapy, but those successes may erode when some wait too long into the course of their disease to get treatment -- whether because they don't know they are infected with HIV, aren't sure how to access the health care system or have competing needs like mental health or substance abuse issues.

Dr. Gebo and her team's research, published in the December issue of the journal Medical Care, reviewed medical records of 8,348 patients at nine HIV clinics across the United States between 2000 and 2007. They found that more than 43 percent of patients were considered late entrants into the health care system, presenting at a clinic with extremely weakened immune systems, characterized by having CD4 counts below 200. CD4 cells are keys to a healthy immune system -- healthy people have counts between 800 and 1,000. When CD4 cells are damaged, as they are by HIV, counts can fall dramatically, making patients more susceptible to infection and certain types of cancer.

Low CD4 counts "make it more likely that patients are going to have complications and more likely that their CD4 counts won't ever recover to normal levels even with antiretroviral treatment," Gebo says. Previous studies have shown that those who come to care late in the course of their disease have shorter survival and benefit less from antiretroviral therapy.

Gebo and her colleagues found that the average difference in cumulative treatment expenditures between early and late presenters ranged from $27,275 to $61,615 higher over the course of the first seven to eight years of treatment. Costs are higher for the late presenters because they tend to be sicker than early presenters, particularly the first year of treatment -- and the cost gap doesn't shrink over time, she says. Late presenters are hospitalized more often, need to be put on costly antiretroviral therapy and antibiotics, and often must be treated for other diseases that have been exacerbated by a weakened immune system.

The study was supported by the Agency for Healthcare Research and Quality and the National Institutes of Aging and Drug Abuse. Richard D. Moore, M.D., M.H.Sc., a professor of general internal medicine at Johns Hopkins, also contributed to the research.

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UNAIDS Pushes Simpler Treatment Plan. 24/11/10

Could save 10 million more lives than conventional approaches over the next 15 years.

Health-e

By Kerry Cullinan
24 November 2010

UNAIDS is promoting a new approach to HIV treatment, which it estimates could save 10 million more lives than conventional approaches over the next 15 years.

The organisation released details of the new plan it is working on with governments and other stakeholders worldwide at the release of its Global HIV/AIDS report yesterday.

Called “Treatment 2.0”, the approach is aimed “reducing treatment costs, making treatment regimens simpler and smarter, reducing the burden on health systems and improving the quality of life for people living with HIV and their families.”

At present, some 33.3 million people worldwide are living with HIV and almost half of these need antiretroviral treatment. However, only around five million people, or a third of those in need, are on ARVs and the demand for treatment threatens to overwhelm the health budgets of countries in sub-Saharan Africa.“Current approaches to treatment have not been optimal for the 15 million people in need,” according to the UNAIDS Global Report.

“Treatment 2.0—a radically simplified treatment platform— holds promise to simplify treatment and provide all people needing it with a better pill, less likely to lead to resistance, simpler diagnostics and monitoring, easier HIV testing, and more community empowerment. All stakeholders should unite to make this a reality.”

Treatment 2.0 is built on five pillars. The first pillar is the development of a “smarter, better antiretroviral pill” that will be” less toxic, longer-acting and easier to use”.

At present, people usually take a cocktail of three pills twice a day. However, UNAIDS believes it is possible to produce one combination pill that may only need to be taken once a day.

The second pillar of the plan rests on simpler “diagnostic tools” to test patients’ viral loads and CD4 counts (measure of immunity) that don’t rely on complicated equipment and specialised laboratory technicians. This would cut costs and make it easier for people to get access to treatment.

Thirdly, UNAIDS also calls for a reduction in the cost of ARV medicine so that they are “more affordable”.

Simpler pills and tests should allow service delivery to be decentralized and integrated into other services, the fourth point in the UNAIDS plan.

The final pillar is community mobilization, aimed at encouraging people to get ARV treatment and to adhere to treatment.

“Greater involvement of community based organisations in treatment maintenance, adherence support and monitoring will reduce the burden on health systems,” notes UNAIDS.

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Whoonga a New Challenge in AIDS War. 22/11/10

ARVs mixed with marijuana and smoked

22 November 2010

Johannesburg - Aids patients in South Africa are being robbed of their lifesaving drugs so that they can be mixed with marijuana and smoked, authorities and health experts say.

The concoction is called "whoonga" - less a word than an exclamation - and it adds a bizarre twist to the war on Aids in the world's worst-affected country just as it embarks on a massive distribution of medications.

Whoonga's spread is so far limited to eastern KwaZulu-Natal, South Africa's most Aids-stricken province, but Aids and addiction specialists worry that it could reach other parts of the country.

There's no evidence that any ingredient of the Aids drug cocktail is addictive or does anything to enhance the marijuana high. Whoonga smokers may be fooling themselves into believing the Aids drugs are giving them a high, when it's really some other ingredient, says Dr Njabulo Mabaso, an Aids expert.

Aids is already a source of damaging myths in South Africa, such as that the disease can be prevented by sleeping with a virgin or showering after sex with an HIV-positive partner.

Widespread

Some drug dealers are suspected of stretching the whoonga mixture with soap powder and even rat poison to increase their profits.

"We are seeing the use of whoonga in communities and it's very widespread. It's a substance that is openly spoken about in communities," says Lihle Dlamini of the Treatment Action Campaign, which has lobbied hard to improve the government's response to Aids.

Drug dealers "are taking this treatment that is supposed to assist people living with HIV and abusing it," she says.

In Durban, Thamsanqa Langa said he didn't know what whoonga was when dealers first started offering the cream-colored powder at R20 a smoke.

It smelled to him of vinegar, said Langa, a soft-spoken 30-year-old of few words.

At first it just quietened him more. "You feel like you can say nothing. You can just sit in a quiet place, not talking."

But after a few days, Langa said, he started having powerful headaches, stomach pains and night sweats. When he went back to dealers, "They said, 'You need to smoke more, keep on smoking,"' Langa recalled in an interview. "That's how I got hooked."

He mooched Aids drugs from HIV-infected friends, robbed houses, became a dealer and missed so many workdays that he lost his factory job. He says he smoked whoonga for four years until he gave it up in March.

Patients robbed outside hospitals

Vincent Ndunge, a police spokesperson in KwaZulu-Natal, said whoonga was first noticed two or three years ago when officers found gangs were robbing people of medication as they left hospitals.

Initially users crushed the pills and smoked them straight, but added other substances later, Ndunge said.

Carol du Toit of the National Council on Alcoholism and Drug Dependence, a private organisation, also says patients are being mugged for their medications or selling them, and that Aids clinics are being robbed. She says staff of her private organisation are seeing increasing numbers of whoonga users, many of whom also test positive for heroin.

She reports anecdotal evidence of whoonga use spreading beyond KwaZulu-Natal, the country's most welfare-dependent province. But police in Gauteng say they have not come across the drug.

Foreign experts say they have not heard of such abuse outside South Africa, and are unaware of research into whether Aids drugs can add anything to a marijuana high.

Patrick Abok, a medical officer specialising in HIV for the World Health Organisation's South Africa office, said the UN agency had no information on whoonga, and referred questions to South African groups.

Mabaso, the doctor who helps run a Durban clinic supported by the US-based Aids Healthcare Foundation, said one component of the Aids cocktail causes hallucinations in some patients, but there's no firm reason to believe it has that effect on addicts. He said Langa could have been suffering from withdrawal symptoms.

South Africa, a nation of about 50 million, has an estimated 5.7 million people infected with HIV. Since taking office last year, President Jacob Zuma has sought to invigorate the previous government's foundering effort, and doctors and nurses are being brought out of retirement and medical students mobilised for an ambitious testing and treatment campaign.

Strict regimen

Aids drugs must follow a strict regimen, and Dlamini worries that the theft or sale of medication can be disruptive. And if clinics are forced to replenish their supplies at a faster rate, their budgets could collapse, she said.

Thokozani Sokhulu, a community activist who started "Project Whoonga" this year, says he has helped about 20 addicts by getting them into rehab and finding them jobs or training. He has also made a short film to warn young people off whoonga. Its stars include Langa, the recovering whoonga smoker.

The larger problem is the province's dire economic straits - 125 000 jobs lost in the global recession, and the poverty that young unemployed men face in places like Kwadebeka, a Durban neighbourhood with no electricity or running water where Sokhulu and Langa work together to help addicts.

"The main problem is unemployment," Sokhulu said. "It's when they're hanging around all day with nothing to do - that's when they get hooked."

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All HIV Patients to get Second-line Treatment Free. 13/11/10

This major policy shift was finalised by NACO on Thursday night.

13 November 2010

New Delhi: All HIV patients put on first line antiretroviral therapy (ART) before 2004 but who became resistant to those drugs will now receive the life saving second line treatment free of cost from the National AIDS Control Organisation (NACO).

This is irrespective of whether the patients were receiving first line ART in a government centre or a private hospital. This major policy shift was finalised by NACO on Thursday night.

Till now, NACO only provided second line treatment to those HIV patients who were part of its ART centres and had become resistant to first line drugs. Those patients on first line treatment in private hospitals or clinics were not eligible.

Second line treatment is tremendously expensive and not affordable for the common man. Also, it was only available in NACO's ART centres. So, patients who did not get first line treatment in NACO's ART centres perished if they became resistant.

Solicitor general Gopal Subramaniam informed a Supreme Court Bench comprising Chief Justice S H Kapadia, Justices K S Radhakrishnan and Swatanter Kumar that the health ministry took this decision on Friday. He informed the SC that details of the decision would be intimated through an affidavit in two weeks.

So what happens to those who were put on first line ART post-2004 but have become resistant to first line drugs? Expert committees in the 10 centres of excellence presently in charge of giving second line treatment will take a call.

ART is the only known treatment that inhibits HIV. The drugs slow down the replication of HIV and immune deterioration is delayed leading to an improvement in the survival and quality of life.

While first line drugs cost NACO Rs 5,000 per patient per year, second line cost them Rs 35,000 per patient per year. Patients, however, get the treatment free of charge.

India is home to an estimated 2.3 million HIV patients of which 6 lakh would require to be on ART. At present, 3.55 lakh HIV patients are receiving first line treatment in 285 NACO ART centres.

Ten centres have rolled out second line ART to 1,701 HIV patients. Five more centres in Nagpur, Pune, Salem, Aurangabad and Surat have been trained to start second line ART while two centres in Vijayawada and Hubli are being prepared.

India rolled out second line ART for the first time on December 1, 2008 in Mumbai's J J Hospital and Chennai's Tambaram ART centre.

Resistance to first line treatment mainly happens because of poor adherence to the treatment regimen. If not put on second line immediately, most of these patients die within a few years.

A CD-4 count test is used to gauge immunity levels of an HIV-infected patient and to assess whether damage caused by the virus requires life-saving ART. The CD-4 count in healthy adults ranges from 500 to 1,500 cells per cubic millimetre of blood. In HIV infected people, it goes down by 60 cells per cubic millimetre of blood per year as HIV progresses. ART is administered when an HIV positive person registers a CD-4 count under 200.

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AIDS Drugs – For Profit Or Not? 11/11/10

It was taboo to even mention market forces when discussing pharmaceuticals for poor countries.

Forbes

By Josh Ruxin
11 November 2010

Not too long ago – as recently as the late 1990s– it was taboo in international development circles to even mention market forces when discussing pharmaceuticals for poor countries.  The doctrine was clear: the free market must be kept out; the international drug trade was exploitative, destructive, and offered little to help the poor.

Drugs to treat HIV and AIDS – then costing more than $15,000 per person, per year – primarily drove the debate.  Most in the development industry vociferously agreed that doctors and drugs had to be supplied, but no one could cope with the astronomical prices involved. Eventually, as it had to, the discussion came to center on how to reduce the cost of drugs so that those with the greatest need – the world’s poorest – could get access to life-saving medicines that would protect their health and slow the pandemic’s death march.

Drug companies argued that poor nations, which were without question bearing the brunt of the scourge, didn’t have the “absorptive capacity” to deliver AIDS drugs efficiently and effectively to patients.  Some argued that patients in rural communities often lived so far from health centers that healthcare providers would not be able to confirm that antiretroviral drugs were taken daily. One development official famously remarked that Africans could not take AIDS drugs correctly because they did not own watches. Drug companies were also concerned about parallel imports: the practice of allowing legal products, in this case pharmaceuticals priced at one level in one country, into another country without the consent of the patent holder. At the turn of this century, however, the expansion of the AIDS pandemic, the corresponding fortitude of AIDS activists, and proof that AIDS drugs could be successfully deployed even in poor settings, put such concerns on the back burner and treatment in front.

In response to global frustration that effective treatments for a killer disease were inaccessible to most of the people who needed them, the Global Fund to Fight AIDS, Tuberculosis and Malaria was established in 2002, and the Bush administration created the President’s Emergency Plan for AIDS Relief, known as PEPFAR.  Activists argued that if all those who needed AIDS drugs could get them via this kind of funding, the very increase in the scale of production would drive drug costs down, which would in turn fuel further market growth, creating a virtuous cycle.  The activists, buttressed by impressive strategic work by the Clinton Foundation, were right.  Even today, prices continue to fall and demand is growing steadily.

Today a year of HIV/AIDS medication costs less than $100. Generic drug companies largely drove this change.  By some estimates, generics account for more than 90% of the market for AIDS medications.  How exactly did this happen?  It was a complex brew of developments that included overcoming patent barriers to produce and sell the drugs in developing countries.  Branded companies played a role by issuing more and more voluntary licenses and by refraining from seeking patents in many low-income countries. Meanwhile, makers of generics developed more efficient manufacturing processes and negotiated bulk discounts on raw materials.  This progress rapidly helped to shift the old paradigm of low volume/high prices to a new one of high volume/low prices.  If this shift hadn’t happened, millions would have died, and drug companies – both branded and generic – would have profited much less.  It was a classic example of doing well by doing good.

Nevertheless, the World Health Organization estimates that a third of the world’s population still lacks access to the most basic and necessary drugs, not just for HIV and AIDS but for all ailments that afflict basic health.  In Africa and Asia, that number increases to 50 percent.  Filling the void too often, particularly in Asia, are cheap counterfeits – sometimes nothing more than placebos and sometimes hhhhhh   armful substances.

In an effort to protect both patients and patent holders and to harmonize patent protection for various types of goods, World Trade Organization members established minimum standards for protecting and enforcing intellectual property.  The agreement they drafted, officially called the Agreement on Trade Related Aspects of Intellectual Property Rights (better known as known as TRIPS), also allows some flexibility in implementation, letting countries limit patent owners’ exclusive rights under certain conditions – such as when dealing with immediate and emerging public health needs.

While TRIPS should enhance incentives for research and development for new drugs, there are still viable concerns that more stringent patent protection will push drug prices higher than advocates would like them to be (i.e. higher than necessary but not necessarily higher than today’s prices). Since TRIPS was instituted, the next generation of HIV and AIDS drugs  has become available, but how the agreement will affect their pricing remains to be seen.  While the HIV/AIDS disease mutates, the effectiveness of the old guard of first-line drugs decreases, but there’s a reasonable concern that the new and improved drugs might command unaffordable prices.

Clearly, the World Trade Organization is an institution whose ideology has been largely, if not completely, influenced by developed countries.  Even though TRIPS offers a framework for big drug companies and developing nations to balance their respective needs, the current system remains deeply flawed. As the AIDS pandemic continues to grow, the vehicles for determining fair access and pricing and access are still not in place.

The debate of a dozen years ago still remains: Should the market have a place in finding health solutions for the world’s poorest people? Although the lack of functional, sustainable healthcare systems – a core foundation for economic development and personal prosperity – plays a far-reaching role in the future of the developing world, we still need to get the pharmaceutical issues right.  Access to life-saving, essential medicines must be improved.  We have to do better. The question is how.

One success I’ve observed on the ground in Rwanda is what happens when a government takes seriously its role as importer of all major essential drugs.  This virtually eliminates counterfeits, and ensures that the health system has the low-cost, high-quality drugs it needs.  Other countries would do well to heed Rwanda’s example, and the pharmaceutical companies may wish to promote this example in other markets.  It’s one way to help profits and health move in the same direction.

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Mobile Phone Messages Improve Adherence and HIV Control in Kenyan trial. 10/11/10

A text message from a clinic each week resulted in better adherence and a higher level of viral load suppression

10 November 2010

A text message from a clinic each week resulted in better adherence and a higher level of viral load suppression among people with HIV after starting antiretroviral treatment in Kenya, a randomised controlled trial has shown.

The results were published in the Online First section of The Lancet this week. The trial was sponsored by the US President’s Emergency Plan for AIDS Relief (PEPFAR).

The intervention cost around 20 cents per patient each month, and would potentially allow one nurse to monitor adherence and other issues in 1000 patients each month, the researchers calculated.

Mobile phones are emerging as a new tool in health care. In sub-Saharan Africa mobile phone networks have expanded to cover much of the continent, and phone ownership is growing exponentially.

The Kenyan study is the first randomised study to test whether sending a reminder message sent to patients taking antiretroviral drugs in sub-Saharan Africa not only improves adherence, but also has a long-term effect on responses to treatment.

The study was conducted at two clinics in Nairobi (one serving a very low income area and one a more prosperous district) and at one clinic in a rural district.  

It recruited patients starting ART for the first time who owned a mobile phone (88%) or who had access to a shared phone (12%). Patients paid for their own air time and text messages.

The study recruited 538 participants eligible for antiretroviral therapy under Kenyan national guidelines in 2007 and 2008, and participants were randomised either to the text message group (n=273) or the standard care group (n=265).

Patients received structured adherence counselling prior to starting treatment, and those in the message group were told to report if they had any problems with adherence in responses to their weekly text message from the clinic.

Typically, the slogan "Mambo?" was sent, which is Kiswahili for "How are you?" The health workers used multiple recipient (bulk) messaging functions to improve efficiency. Patients in the intervention group were instructed to respond within 48 hours that either they were doing well ("Sawa") or that they had a problem ("Shida"). The clinician then called patients who said they had a problem or who failed to respond within two days.

The primary outcomes measured in this study were self-reported ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits) and viral load suppression below 400 copies/ml at 12 months.

During the study 114 patients dropped out, including 44 patients lost to follow-up and 55 who died. There was no significant difference in loss-to-follow-up rates between the two groups.

Intent to treat analysis, which evaluated outcomes in everyone recruited to the study, with lost patients counted as failures, showed that optimal adherence to ART was reported in 168 of 273 (62%) patients receiving the message intervention compared with 132 of 265 (50%) in the control group. Suppressed viral loads were reported in 156 of 273 patients (57%) in the message group and 128 of 265 (48%) in the control group.

On treatment analysis, which counted only those who remained in the study until the end, showed no significant difference in adherence (91%) but a significantly higher rate of viral suppression in the message group (75% vs 66%, p=0.047).

After adjustment for baseline factors such as age, CD4 count, gender, literacy and income, adherence in the message group remained significantly better (odds ratio 0.57, 95% confidence interval .0.40 – 0.83, p=0.0028). The relationship between message receipt and viral load suppression was less strong in the adjusted analysis, and was on the borderline of statistical significance (odds ratio 0.70, CI 0.50 – 1.01, p=0.058).

Overall, an average of 3.3% of patients sent messages indicating that they needed help each week, and this proportion declined from 6% in the first three months to 2% afterwards (p<0.0001).

No breaches of confidentiality as a result of text messaging occurred during the study, and patients were highly satisfied with the service. 98% said they would recommend it to a friend, and all but three patients receiving the service at the end of the study said they wanted it to continue. Many patients said they valued the service because they felt “like someone cares”.

The study had a very low impact on health care staff; it required no advance training to deliver the service, and the researchers estimated that one nurse could manage 1000 patients and expect to call only 33 patients each week.

The researchers say that one extra patient would achieve adherence for every nine patients using the SMS service; while one extra person would achieve viral suppression for every 12 treated in the SMS group.

In conclusion, say the authors, the study has a number of important implications.

It is the first to show that an adherence intervention has an effect on virological failure rates, and it is a very low-cost intervention. If it was applied to everyone receiving ART in Kenya through PEPFAR funding (297,000 in 2009), they calculate, it would result in an additional 26,354 people with suppressed viral load.

The authors also note that increasing viral suppression in the population is likely to have a knock-on benefit for HIV prevention.

In an accompanying editorial comment, Jeffrey Stringer and Benjamin Chi of the Centre for Infectious Disease Research in Zambia say that policy makers should now consider bringing the intervention to scale, but say a number of questions still need to investigated before copying the intervention.

At the moment, they say, it’s not clear how the once-weekly message affected adherence. Also, it’s not clear how it would work in other countries, particularly where fewer people own phones. Would it be necessary to provide phones or subsidise airtime?

They also say think that cost-effectiveness needs to be studied, since if it was applied across the whole national treatment programme in Kenya, it would take up 1% of the current budget at a cost of around $2.6 million. But this might be cost-effective given the cost of second-line treatment, they say.

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One-pill Regimen Improves Adherence and Reduces Hospitalisation in Insured US Patients. 9/11/10

People taking a single-pill daily drug regimen do appear to have better adherence

AIDSMap

Bu Gus Cairns
9 November 2010

People taking a single-pill daily drug regimen do appear to have better adherence than people taking more pills a day, according to a study of a large database of patients in the USA presented this week at the Tenth Congress on Drug Therapy in HIV Infection in Glasgow..

This improved adherence also translated into better health, according to the study, which was sponsored by Gilead, one of the manufacturers of the once-a-day tenofovir/FTC-efavirenz pill Atripla. Patients taking one pill a day had fewer hospitalisations, even when other factors were controlled for.

Judith Meyers of the health consultancy RTI Health Solutions told the conference that the study investigated 7073 patients on the Life Links claims database, a group of [patients insured by a commercial insurer, who were diagnosed with HIV between June 2006 and December 2008 and received a complete antiretroviral therapy (cART) regimen for at least 90 days. This was defined as regimens of at least three drugs and therefore excluded 1829 patients who were on what was described as incomplete ART, which included protease inhibitor monotherapy and dual therapy.

Adherence was calculated by dividing the number of days covered by refilled prescriptions by the total days people were on treatment.

It was found that a third of patients (2365) were on one pill a day, six per cent (411) on two a day (this would most likely be efavirenz plus one of the two-NRTI combination pills) and the remainder (4297) on three or more, which included all the patients on protease inhibitors.

Not surprisingly a higher proportion of patients on one pill (42%) were on their first cART regimen compared with 25% on two drugs and 20% on three or more.

Of the patients on three or more drugs, a third were on NNRTI-based regimens and two-thirds on PI-based ones. Only 50% of these were on boosted PIs.

Only a minority of patients achieved better than 95% adherence, but more of them on one-pill regimen did so: 47% on one pill, 41% on two and 34% on three or more. This pattern persisted at lower adherence rates: for instance 72%, 68% and 62% achieved more than 90% adherence on one, two and three pills respectively.

A multiple regression analysis, controlling for factors like drink/drug use, length of treatment, gender etc found that patients on one pill were 61% more likely to take more than 95% of doses than patients taking three or more pills a day. In contrast patients with drug or alcohol abuse were 40% less likely.

Adherence clearly translated into better health, with patients 40% less likely to be admitted to hospital over the study period if they achieved over 95% adherence. In contrast patients with drink/drugs problems were nearly three times as likely to be admitted to hospital (192% higher), patients with psychological illness 40% more likely, and women 30% more likely.

In univariate analysis (not controlling for confounders) taking a one-pill regimen was directly associated with 20% fewer hospitalisations, and in multivariate analysis this correlation was slightly strengthened, with 24% fewer hospitalisations .this was strongly statistically significant (p=0.003). In absolute terms and controlling for all other variables the hospitalisation rate was 7.7% in patients taking one pill versus 9.9% in patients taking two or more.

The limitation of this study, Meyers said, was that there was no way of telling why patients had been selected for their particular regimen, and the difference in hospitalisations could have been due to patients who were less sick being selected for a one-pill regimen.

Conversely, it was pointed out that as there is only one current one-pill-a-day regimen (Atripla) this was essentially a study comparing the performance of that particular combination of drugs against other regimens rather than one pill versus more, and the results could have been due to the intrinsically greater efficacy of tenofovir/FTC/efavirenz.

The study was also of patients who have private health insurance; it may not be possible to generalise the results to the significant proportion of poorer and unemployed patients in the USA who rely on public health resources.

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Study Confirms that the Sooner Treatment is Started the Better. 9/11/10

36% less likely to experience treatment failure

AIDSMap

By Gus Cairns
9 November 2010

A study presented at the Tenth International Congress on Drug Therapy in HIV Infection in Glasgow has found that patients who started antiretroviral combination therapy (cART) within the first year after diagnosis were 36% less likely to experience treatment failure, and 65% less likely to develop HIV drug resistance on treatment, than patients in general.

The patients studied were in CASCADE, a unified ‘cohort of cohorts’ in 13 European countries, Australia, Canada and several countries in Africa. CASCADE, which stands for Concerted Action from Seroconversion to AIDS and Death in Europe, only includes patients with a known date of HIV infection (seroconversion). The current study examined the clinical history of 1223 patients who had started cART less than a year after seroconversion and included patients from 1997 onwards: it therefore included many patients who had started on what would now be regarded as suboptimal regimens.

The primary outcomes studied were the proportion of patients who developed virological treatment failure (defined as at least two consecutive viral load tests over 400 on treatment) and the proportion who developed HIV drug resistance.

Of the 1223 patients, 85% were male, with a median age of 34. Their average CD4 count at the start of therapy was 432; a majority would have been excluded from starting therapy if doctors had conformed to the recommendations of the current BHIVA and EACS treatment guidelines, though not US ones.

One hundred and fifty-one patients had drug resistance tests before they started cART, and seven patients (4.6%) turned out to have primary (transmitted) drug resistance.

The fact that this is a historical cohort was underlined by the fact that 71% started on protease-inhibitor-based cART. Sixty per cent interrupted their therapy at some point and the average time to interruption of therapy was one year.

In terms of time to virological failure, by four years after the start of therapy 11% had experienced failure and 3% (of the whole group) had confirmed drug resistance that had been detected. This latter figure may be higher in truth, because only half of the patients who failed had drug resistance tests.

Eight years after the start of therapy, 18% had failed treatment and 6% had confirmed drug resistance. These figures are lower than those seen in a survey of the long-term treatment history of a cohort of all patients on treatment (Cozzi-Lepri): in this study, after eight years, 28% had failed treatment and 17% had confirmed drug resistance.

Presenter Sara Lodi commented that most failures happened in the first two years of treatment. The older people were when they were diagnosed and started treatment, the less likely they were to fail treatment: there was 30% less treatment failure for every decade of age. And there was 8% less failure and 26% less drug resistance for every 100-cell increase in CD4 count at the start of treatment.

Delegates were reminded that HIV treatments became considerably more effective and tolerable over the time period surveyed in the study. One reminder was that patients who had taken unboosted protease inhibitor regimens were nearly three times (192%) more likely to have failed treatment than patients with other treatment histories.

Lodi’s cautious conclusion was that “Our data do not support early initiation of antiretrovirals being associated with high levels of drug resistance”.

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HIV Detectable in CSF of 10% of Patients taking Successful Antiretroviral Treatment. 17/11/10

Detectable viral load – or viral escape -  in cerebrospinal fluid

AIDSMap

17 November 2010

Ten per cent of patients taking antiretroviral therapy who have an undetectable viral load in their blood have detectable levels of HIV in their cerebrospinal fluids, Swedish and US investigators report in the online edition of the Journal of Infectious Diseases.

Detectable viral load – or viral escape -  in cerebrospinal fluid (CSF) was associated with evidence of immune activation in the brain, longer duration of antiretroviral therapy and treatment interruptions.

“Previous studies have shown that CSF HIV-1 RNA generally responds well to antiretroviral therapy”, comment the authors. However, they add, “our findings…suggest that viral escape in CSF, even in subjects with successful systemic treatment with contemporary regimens, is a more common occurrence than previously reported.”

The author of an editorial that accompanies the paper “congratulated” the authors on their research, and writes: “It is concerning that this ongoing viral presence represents a serious threat to brain injury over the many years that patients are expected to live.”

Thanks to antiretroviral therapy the prognosis of many HIV-positive patients is excellent. This treatment suppresses HIV replication in the blood to very low levels allowing the immune system to recover and fight infections. Successful therapy also leads to reductions in localised and systemic inflammation.

However, not all anti-HIV drugs cross the blood-brain barrier or blood-CSF barrier, and few studies have looked at the presence of a detectable viral load in CSF in patients who are taking HIV therapy and have an undetectable viral load in their blood.

Therefore investigators in Gothenburg, Sweden, and San Francisco, California, designed a cross-sectional, or snapshot, study involving 67 patients. All the patients were taking modern anti-HIV drugs and had had an undetectable viral load in their blood for at least six months. None had any neurological symptoms. The patients were recruited between 2002 and 2010.

A total of seven (10%) of individuals had detectable HIV in their CSF. The median CSF viral load was 121 copies/ml (range 52-860 copies/ml).

Detectable CSF was associated with increased inflammation in the brain. Levels of CSF neopterin (a marker of inflammation and macrophage activation) were significantly higher in patients with detectable CSF viral load than those with undetectable CSF viral load (9.2 vs. 5.1 nmol/ml, p = 0.03).

In addiiton, 71% of individuals with detectable levels of HIV in their CSF had neopterin levels above the ”normal” value (5.8 nmol/l) compared to 40% of patients with undetectable CSF viral load.

Blood viral load did not differ significantly between the patients with detectable and undetectable CSF viral load.

Longer duration of HIV treatment had a significant association with detectable viral load in CSF. Individuals with detectable HIV in their CSF had been taking treatment for a median of 77 months, compared to a median of 35 months (p = 0.002) for individuals with undetectable CSF load.

In addition, detectable CSF viral load was associated with a greater number of viral load “blips”  - transient increases in blood viral load above 50 copies/ml. Those with detectable HIV in their CSF had a median of 2.5 blips compared to a median of zero for those with fully suppressed CSF viral load (p < 0.01). The investigators suggest that this could be related to adherence.

Treatment interruptions were also more common among those with detectable CSF virus (p < 0.01). The investigators believe that such interruptions were leading to the “intermittent reseeding” of viral load in the brain and CSG.

There was no evidence that any anti-HIV drug was associated with detectable CSF load. Nor was penetration of drugs into CSF and the brain significant.

“We demonstrate that 10% of subjects had CSF HIV-1 RNA >50 copies/ml”, comment the investigators.

They add, “subjects with detectable CSF virus had significantly longer exposure to ART and higher levels of intrathecal immune activation; treatment interruptions were also more common in these subjects”. 

The investigators are uncertain of the clinical significance of their findings.

None of the patients with detectable CSF viral load had neurological symptoms, “suggesting that viral escape in CSF may, at least in the short term, be clinically benign or silent in treated individuals.”

Aware of that their study had a cross-sectional design and small sample size, the researchers conclude by calling for larger, longitudinal studies to examine the issues raised by their research.

This call is echoed by the author of the accompanying editorial, who was especially concerned that ongoing HIV replication in the brain could have an impact on the neurocognitive performance of HIV-infected individuals as they age.

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Vacc-4x Shows Statictically Significant Reduction in Viral Load. 11/10

Study designed to test HIV-patients' ability to stay off antiretroviral therapy (ART) after having been immunized with Vacc-4x

November 2010

Further analysis of Vacc-4x phase IIb study shows a statistically significant reduction in viral load over placebo – Bionor Pharma reverses decision to put Vacc-4x on hold

After further analyses of the international, randomized, double-blind, placebo-controlled multi-center phase IIb study of Bionor Pharma's therapeutic HIV-vaccine candidate, Vacc-4x, the Company reports an unexpected statistically significant reduction in viral load (amount of HIV virus) at the end of the study period for patients on the vaccine compared to the placebo group.

The study was designed to test HIV-patients' ability to stay off antiretroviral therapy (ART) after having been immunized with Vacc-4x. Although the study did not meet its primary endpoints, as announced October 1, the findings from the additional analysis discovered that treatment difference with regard to viral load was statistically significant both within the study period and when compared to the viral load prior to ever starting ART. In patients who received immunization, viral load never returned to its pre-ART level, which normally happens when being taken off ART.

Due to the new findings, the Company has reversed its decision to stop development of Vacc-4x. Along with upcoming immunological data, these findings are expected to become the basis for the future positioning of Vacc-4x as a viable therapeutic HIV-vaccine.

As announced October 1, the Vacc-4x phase IIB study did not meet its two primary endpoints; i.e. no difference between the two groups with regard to the number of patients that needed resumption of ART nor any difference in immune cell (CD4) counts at the end of the ART-free period.

Still, the effect on viral load is by health authorities and most clinical experts seen as more important clinically for the treatment of HIV-patients than the effect on CD4-counts. Change in viral load between Vacc-4x and placebo during the study period was among the secondary endpoints in the phase IIB study. A statistically significant treatment difference with regard to viral load was found for the whole patient population (p=0.028), and a statistically significant effect was reproduced also in the sub-set of patients that did not resume ART (P=0.0012).

Additional support for the effect of Vacc-4x on viral load has come from a pooled post-hoc analysis including pre-ART viral loads. Pre-ART level is an important set-point since viral load normally migrates back to this level after ART interruption.  Company researchers discovered on further review that patients blinded and randomly assigned to Vacc-4x treatment group had a pre-ART viral load three times higher than that of patients assigned to the placebo group. The study showed that viral load in patients who received immunization never returned to its pre-ART level. A statistically significant reduction in viral load from the pre-ART level (0.55 log, p=0.0003) was found in patients treated with Vacc-4x compared to a non-statistically significant reduction in viral load (0.08 log, p=0.89) in patients in the placebo group.

“These follow up findings on viral load reduction in the Vacc-4x arm compared to placebo are positive and very encouraging,” said Professor Dr. med. Jürgen Rockstroh, Oberarzt an der Medizinischen Universitätsklinik, Innere-Rheuma-Tropen Ambulanz, Bonn, Germany. “It is therefore important in follow on studies to investigate whether Vacc-4x in combination with ART could reduce the viral set-point and allow extended periods without HIV medicine.”

 “Patients starting on antiretrovirals see the viral load effectively reduced, but this is dependent on daily treatment, and we know that HIV remains in the reservoirs,” said Richard Pollard MD, Division Chief of Infectious Disease, University of California Davis Center for AIDS Research, Education, and Services and the principle investigator in the trial.  “A therapeutic HIV vaccine like Vacc-4x reducing the viral load set-point, could have significant implications for future HIV management used in combination with ART.  More research is needed to confirm this hypothesis.”

 “I am pleased to see that immunization with Vacc-4x, a candidate therapeutic vaccine under clinical development, has shown the ability to reduce virus levels in blood of chronically HIV infected patients,” said Professor Giuseppe Pantaleo, Professor of Medicine, Chief Division of Immunology and Allergy and Head of the Laboratory of AIDS Pathogenesis, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. These results are important since they indicate that better virus control may be achieved through immunological intervention. Vacc-4x through a different antiviral mechanism may represent a novel intervention to complement antiviral therapy.”

“The new analysis gives indications that Vacc-4x has an important effect on viral load despite the failure to reach our primary endpoints in the phase IIb study,” said Bionor Pharma CEO Henrik Lund. “While post-hoc analyses are subject to statistical limitations, they are commonly used in vaccine trials due to the complex nature of data interpretation.”

The full immunological analysis and long term data will give us a better basis for evaluating the outcome and implications for the positioning of Vacc-4x as a therapeutic product for HIV-patients. A possible application of Vacc-4x is a combination therapy with repeated ART-Vacc-4x together with analytical treatment interruptions in order to establish a functional cure.”

 

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Nurse Attitudes, Clinic Experience, Key to Improving Care and Retention in ARV Programmes. 28/10/10

People with HIV can receive excellent care and adhere well to antiretroviral treatment despite staff and resource shortages

AIDSMap

By Keith Alcorn
28 October 2010

People with HIV can receive excellent care and adhere well to antiretroviral treatment despite staff and resource shortages, but the attitudes and performance of nurses and patients’ experiences of the clinic are often crucial in determining how satisfied patients are with the care they receive – and whether they keep coming back to the clinic, a study conducted in Zimbabwe shows.

Catherine Campbell and colleagues reported the results of a qualitative study of the perceptions of nurses and their patients on antiretroviral treatment at three sites in rural Zimbabwe published in the online edition of International Journal of Nursing Studies.

Both nurses and patients stressed the importance of nurse kindness, understanding, confidentiality, the ability to listen, acceptance of HIV like any other disease, and adherence.

Different expectations and priorities presented challenges to both nurses and patients. Nurses, for example, often failed to notice how distressing and difficult long wait-times and frequent hospital visits were for patients.

A significant source of frustration for both patients and staff was the unpredictability of key services including payment for services, time to wait until being seen and the availability of drugs and./or doctor’s services.

With the increasing availability and affordability of antiretroviral treatment in sub-Saharan Africa HIV can be viewed as a chronic, manageable condition rather than one of acute and predominantly palliative care.

The World Health Organization recommends the delivery of antiretroviral treatment through health centres as part of a package of care that includes co-trimoxazole prophylaxis, counselling, the management of opportunistic infections and other co-morbidities and nutritional support.

Following initiation of ART by a doctor, follow-up care is given primarily by nurses, who are increasingly taking on many of the responsibilities previously undertaken by doctors (task shifting).

The authors stress that the rollout of ART provides both opportunities and challenges for healthcare workers, “heralding a new era of HIV nursing in Africa.” The availability of ART means that nurses will develop a different kind of relationship with patients interacting more frequently over a long period of time.

To make the most of these positive opportunities requires, according to the authors, a greater understanding of what these changes bring, in particular in terms of how best to support nurses and patients.

Their case-study looked at how patients and nurses viewed the changes and challenges brought about by ART. Improvement of care in resource-poor settings requires an understanding of what nurses and patients consider to be good clinical care, the authors note. Looking at the differences in their perceptions is critical to improving care and so contributing to best practices in HIV nursing.

Research, involving interviews and focus groups as well as 100 hours of observation of treatment settings was conducted by four fieldworkers over a period of six weeks in 2009 in rural Zimbabwe at three sites providing free antiretrovirals: a Catholic clinic, an Anglican hospital and a government hospital. The adult HIV infection rate is approximately 20%.  Specifics were excluded to protect the identity of the participants.

A total of 53 patients on ART and 40 carers of children on ART were interviewed and participated in focus groups. During focus groups patients were invited to role-play a ‘good day at the clinic’ and a ‘bad day at the clinic’.

Twenty-five health staff (primarily nurses but including counsellors, pharmacists and a clerk) were interviewed. Because of staff shortages a focus group was only possible at the Anglican hospital.

The overwhelming response by patients and nurses was extremely positive.

High quality of care was the norm in a setting where chronic stress is a given because of critical staff, drugs and/or equipment shortages, lack of respect between the different health cadres and little or no accountability. These findings, the authors stress, are contrary to most research concerns that focus on non-adherence and burn-out. This suggests improved care needs to understand and address differing nurse and patient needs and priorities, they add.

The findings were grouped into five thematic areas:

1)      ideal interaction between nurses and patients
2)      obedience versus adherence
3)      control/distribution of antiretrovirals
4)      HIV clinic availability
5)      ‘grey areas’ surrounding payments and access to service

At all sites both patients and nurses gave critical importance to kindness, confidentiality and not being treated differently (stigmatised). Both patients and nurses said listening was key to good clinical care.

Both nurses and patients recognised the importance of adherence with patients acknowledging nurses instructions as critical. 

However, at times the boundary between adherence and obedience was blurred. Nurses gave orders to patients for no other reason than to show their power over the patients; a way of coping with the stresses of working in a resource-limited and often unpredictable setting, note the authors. For example, a nurse might say “everyone sit down, I won’t serve anyone standing up.”

Efforts to change healthcare worker behaviour in such settings are limited if root causes are not addressed, the authors stress. Yet, in this setting compassionate care was the norm. Understanding what makes this possible in such an environment is critical to help “support future efforts to foster positive staff-patient relationships in resource-poor settings.” 

The area of greatest misunderstandings related to the organisation of the ART programme. Patients were confident in their ability to adhere; wanted fewer visits allowing for receipt of several months of ARVs at a time; struggled to pay the one or two dollar consultation fee, and wanted shorter wait times. The visits usually exhausted their already limited financial and physical resources.

Patients believed a good nurse or pharmacist is one who prescribed several months of ARVs at a time and those who gave out small amounts were seen as bad. The patients did not consider this as the nurse’s desire to closely monitor ART, nor to ARVs often being in short supply. Nurses, in turn, failed to recognise these as sources of stress to the patient.

The authors suggest that finding ways to speed up patient visits on ART review (check-up and refill) days would greatly relieve the considerable stress experienced by patients. They recommend, for example, reviewing ART on more than one or two days a week or increasing staff on high-capacity days.

The authors note almost every patient is poor and in need of nurse or doctor assistance, so staff will be at odds as who to prioritise.  On top of which will be the pressures to help relatives and friends. Dealing with conflicting demands is part of their work routine.

The authors note their findings also suggest that religious faith offers a sense of solidarity requiring further study.

Noting that their study was undertaken when ART had only been introduced into their sites a year previously “limits their understanding of the longer-term evolution of patient-provider relationships in the era of ART.” A follow-up study in 2012 is planned to review these initial findings.

Reference  

Campbell C et al. A ‘good hospital’: nurse and patient perceptions of good clinical care for HIV-positive people on antiretroviral treatment in rural Zimbabwe-a mixed-methods qualitative study. Int J Nurs Stud, 2010. doi:10.1016/j.ijnurstu.2010.07.019

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Trying to Follow the Trail of Missing AIDS Patients. 25/10/10

“The first time I started taking them, I was having the feeling that my heart was pounding and I had no strength."

New York Times

By David Tuller
25 October 2010

Kisumu, Kenya — The young woman perched on the edge of the bed in her tiny hut. She was 29 years old, an AIDS widow who supported herself by frying and selling potato fries by the side of the nearby road.

Yes, she acknowledged to Peter Ouma Mchembere, a young counselor from a local H.I.V./AIDS project, she hadn’t returned to the clinic for her antiretroviral medications in more than a year; no, she didn’t plan to come back anytime soon.

She disliked the drugs, she explained: “The first time I started taking them, I was having the feeling that my heart was pounding and I had no strength.” These days, she said, she chose to rely on prayer instead of medicine to give her strength so she could care for her two young children.

“It’s not bad to pray, but getting care is also important, because this is biological,” advised Peter, who works in Kisumu for Family AIDS Care and Education Services, or Faces. The organization is a joint clinical and research program of the Kenya Medical Research Institute and the University of California, San Francisco.

“It’s very painful,” Peter said to me after we left her home. “She has two kids and they’re at a tender age, and if she dies, who’ll take care of them?”

I was in Kisumu, the largest city in western Kenya, as both a journalist and a public health researcher from U.C. Berkeley. This scruffy but lively port of more than 300,000 people on the eastern shore of Lake Victoria is a regional hub for commerce, transient relationships and H.I.V. infection. About 15 percent of the adults in the region are believed to be infected.

At Peter’s clinic, as elsewhere in Africa, patients who have not come for their medications in recent months are considered to have defaulted from treatment. As a “defaulter tracer,” Peter tries to track them down, find out what’s gone wrong and get them back into treatment, if possible.

Epidemiologists refer to such patients as “lost to follow-up,” and their increasing numbers in sub-Saharan Africa are causing concern among providers of H.I.V. and AIDS care. Interruptions in treatment lead to viral strains that are resistant to the cheapest medications, and to higher rates of illness and death.

Several years ago, during the rapid international expansion of H.I.V. drug distribution, researchers reported very high rates of adherence to treatment in sub-Saharan Africa — as high as or higher than in the United States. More recently, however, studies have found that 15 to 40 percent of those who start treatment are lost to follow-up within one to three years. This unsettling trend has emerged at a difficult time; financing for treatment from the United States and other donors is not keeping pace with the rate of new infections, which has generated waiting lists for the lifesaving medications in some parts of Africa.

At Faces, the loss-to-follow-up rate is around 30 percent, according to Dr. Dennis Osiemo, the organization’s technical adviser for care and treatment. In many instances, he said, problems over which patients have little or no control — like lack of child care, distance from a clinic or the high cost of transportation — force them to miss appointments or drop out of treatment. Others, of course, have died.

But recent research from Uganda found that a significant number of patients designated as lost to follow-up were actually receiving care elsewhere. A similar tracking effort is being started at Faces, but efforts to determine the status of lapsed patients are not always successful. “If a patient is outside the catchment area, it’s very hard to trace them,” Dr. Osiemo said.

H.I.V. programs in Africa are experimenting with various strategies to reduce loss to follow-up — offering a two- or three-month supply of medication per clinic visit, delivering drugs directly to patients’ homes and reimbursing them for transportation costs. Faces is exploring modest projects to raise patients’ income and stabilize their lives, like creating a microfinance system to provide water pumps and other agricultural support to help them grow more crops.

While accompanying Peter on his rounds of the district, I discovered that many cases elude easy solutions — the technological, financial or pharmacological fixes that Western-financed programs seek to carry out.

In search of the defaulted clients on Peter’s list, we rode in matatus — the wheezing, overcrowded minivans that provide cheap local transportation — to outlying neighborhoods, past hundreds of ramshackle storefronts bearing names like Blessed Mum Butchery, Canaan General Retail Shop and the Yes We Can Hair Salon. (President Obama’s ancestral village, Kogelo, is an easy drive from here.)

Peter, a tall, lanky man in his early 20s, lost both his parents to AIDS in 2006. He is supporting two younger brothers and a younger sister, all in their teens, and he struggles to pay their school fees so they can continue their education.

“I know what people are going through, so I have the heart to help them,” he said. He spoke slowly, as if contemplating the import of each word, and wore a black and white rubber bracelet inscribed with the word “friendship.”

Peter says he loves being able to reconnect patients with treatment, but his days can also prove fruitless and frustrating.

On this afternoon, one client was a woman who had stopped taking her young H.I.V.-positive grandson to the clinic every month. When we arrived in their neighborhood, Peter asked passers-by if they knew the family. Most said no.

Finally, a young boy stepped forward, led us across muddy paths and rows of shacks, and pointed out their home. No one was there, and it was clear no one had been for some time. A neighbor said they’d left for somewhere else a month before.

Next was a young disabled patient whose mother used to take her to the clinic. When we located the dwelling, we found the young woman, who was 20, sprawled in the dirt. She appeared to be suffering from serious neurological and cognitive problems.

The woman living next door told Peter that one recent morning she woke up to find that the mother — her sister — had disappeared, with no forwarding information. She knew nothing about her niece’s medical condition, she said, as Peter tried to discuss arrangements to get the girl back into treatment.

But that day it was the decision of the young widow to continue praying instead of returning to the clinic that haunted Peter. Her determination to ignore the medical realities underscored the limitations of his efforts.

When the woman insisted that faith would heal her, Peter challenged her gently. “Even at the clinic, people are praying and still getting medication, because H.I.V. is in the body and blood,” he said.

She acknowledged that she’d recently tested positive a second time, but that did not dissuade her. “I’m still hoping to be tested again and be negative,” she said softly.

Peter and I stood up. He knew there was nothing more to say. He wished her well, encouraged her one last time to return. She smiled and shook her head.

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Drug Safety Bodies Issue Warning on Heart Rhythm Risks with Saquinavir (Invirase). 22/10/10

Saquinavir has been linked to prolonged QT and PR intervals in the heart’s electrical cycle

AIDSMap

Keith Alcorn
22 October 2010

The US Food and Drug Administration and the European Medicines Agency have strengthened their warnings to doctors and patients about the potential of the HIV protease inhibitor saquinavir (Invirase) to cause disturbances in electrical activity in the heart leading to abnormal heart rhythm when the drug is combined with a boosting dose of ritonavir (Norvir).

Saquinavir has been linked to prolonged QT and PR intervals in the heart’s electrical cycle in a study in healthy volunteers.

The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. A prolonged QT interval is a risk factor for cardiac arrhythmias. The PR interval measures a phase of electrical activity that precedes the QT interval.

A prolonged QT interval can lead to a serious abnormal rhythm called torsades de pointes, which can be fatal. A prolonged PR interval can lead to a serious abnormal rhythm called complete heart block. Torsades de pointes and complete heart block have been reported in a very small number of patients taking saquinavir with ritonavir.

Although QT prolongation is likely to be a rare adverse event, the European Medicines Agency now recommends that every patient starting saquinavir should receive electrocardiogram monitoring prior to and after the start of treatment.

The US Food and Drug Administration makes a more detailed recommendation, saying that patients with a QT interval > 450 msec should not receive ritonavir-boosted Invirase. For patients with a QT interval < 450 msec, an on-treatment ECG is suggested after approximately 3 to 4 days of therapy. Patients with a QT interval > 480 msec or with prolongation over pre-treatment by > 20 msec should discontinue saquinavir/ritonavir.

The FDA recommends to anyone taking saquinavir: “Seek immediate care if you experience an abnormal heart rate or rhythm or other symptoms including dizziness, lightheadedness, fainting or heart palpitations.”

The European Medicines Agency also recommend that the dosage of saquinavir for the first week of treatment will be reduced from 1000 mg twice daily to 500 mg twice daily for treatment-naïve patients initiating therapy with saquinavir/ritonavir. The agency says that this dosage adjustment is designed to minimise cardiac risk during the time that the risk is thought to be highest.

This dosage adjustment is not necessary in patients who are switching from other antiretroviral drugs; the European Medicines Agency says the risk of QT prolongation is greatest in people who have never taken antiretroviral drugs before.

The US Food and Drug Administration has made no recommendation regarding dosage adjustment.

Saquinavir’s manufacturer Roche is also planning to conduct a new clinical study to investigate the potential risk of arrhythmia in treatment-naïve patients receiving the reduced starting dose of Invirase in combination with other antiretroviral medications.

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DHMC Doctor’s Study Prompts Global Reaction. 20/10/10

How to treat children who have contracted HIV from their mother

The Dartmouth

By Daniel Bornstein
20 October 2010

The World Health Organization has altered its guidelines after a study — led by Dartmouth-Hitchcock Medical Center pediatrician Paul Palumbo — found the use of a new drug combination in the treatment of pediatric HIV in Africa to be more effective than the traditional approach. Now the researchers must confront the obstacles — most particularly, the cost — of implementation in resource-deprived nations, Palumbo said.

The study addressed the issue of how to treat children who have contracted HIV from their mothers. The study, published this month in the New England Journal of Medicine, found that adding the drug Kaletra to the treatment was more effective in combating HIV infections in babies compared with the more conventionally used method of solely using Nevirapine.

“If a baby gets infected, and they need treatment, then there is the issue of what to actually treat them with,” Palumbo said. “The featured strategy for preventing transmission from an infected mother to her baby is to give a pregnant woman a single dose of Nevirapine when she goes into labor, and then when the baby is born, give the baby Nevirapine.”

This method halves the HIV transmission rate from mother to baby, he said.

Despite the popularity of this approach in Africa, there is a high probability that HIV will eventually develop resistance to Nevirapine, Palumbo said. This danger warranted investigation into whether a different drug could protect newborns against HIV infection.

All the babies in the study — aged six months to three years — were treated with Nevirapine prior to enrollment. The study involved giving some of the babies a dose of Kaletra and some a second dose of Nevirapine and comparing the results, Palumbo said.

In April 2009, an independent group of experts, who were dispatched to clinical trial sites every six months to gauge both the study’s effectiveness and the subjects’ safety, determined that the combination was more effective than the single doses. Currently, the researchers are looking at the effect of Kaletra after no initial dose of Nevirapine.

In response to the study results, the World Health Organization updated its guidelines to recommend the use of Kaletra in treating pediatric HIV patients. With the new guidelines, the next step is to bring the Kaletra-focused approach to the country level, where the health ministries of individual African nations will have to decide whether they want to follow the WHO’s recommendations, Palumbo said.

Because Kaletra costs four to five times more than Nevirapine, Palumbo acknowledged that this would be a challenge for developing countries.

“At the country level they’re still grappling with this,” he said. “They’re dealing with very limited resources.”

Palumbo acknowledged the efforts of the people on the ground, including a physician, nurses, pharmacists, data managers and community leaders, who enabled the study to be put into action.

“Study teams on the ground were critical,” Palumbo, who took a three-day visit to each of the 10 study sites in a total of six African nations, said. “They were very skilled, dedicated people.”

Combating HIV/AIDS is one of the United Nations’ Millennium Development Goals, launched in 2000 to fight global poverty. By 2015, the year the MDGs are to be attained, the goal is to have halted and begun to reverse the spread of HIV/AIDS, according to the UN website.

But Sub-Saharan Africa, where Palumbo conducted his research, remains vulnerable to the HIV/AIDS crisis, according to “The Millennium Development Goals Report 2010,” published by the UN.

Of all new HIV infections in 2008, 72 percent occurred in sub-Saharan Africa, according to the report. Sub-Saharan Africa also accounted for an overwhelming majority of the 17.5 million children worldwide who lost at least one parent to AIDS in 2008.

One of the MDGs related to HIV/AIDS was to have achieved universal access to HIV/AIDS treatment by 2010 for all those who need it, according to the report.

“The rate of new infections continues to outstrip the expansion of treatment, drawing attention to the urgent need to intensify both prevention and treatment measures,” the report said in assessing the failure to meet this target.

Despite the prevalence of HIV/AIDS in Africa, there remains reason for optimism, according to Donna Barry, the policy and advocacy director of Partners In Health, an international health care organization co-founded by College President Jim Yong Kim.

“We’ve seen some incredible success stories [with HIV/AIDS treatment],” Barry said in an interview. “Ten years ago there were none.”

HIV/AIDS treatment is making far more progress than maternal and child health — another one of the MDGs — because so much research has been devoted to HIV/AIDS issues, according to Barry.

At the same time, however, the economic crisis has made it difficult for European donor nations to ensure the necessary funding for AIDS treatment, Barry said.

“If resources aren’t there, the progress is going to be slower than any of us would like,” Barry said.

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New HIV Eradication Study in Progress. 20/10/10

Traditional ARVs can’t target HIV genetic material (HIV DNA) inside this reservoir of infected cells.

20 October 2010

Cytheris has announced the launch and recruitment of a new Phase II study of the company’s interleukin-7 (IL-7) drug—combined with the entry inhibitor Selzentry (maraviroc) and the integrase inhibitor Isentress (raltegravir)—with the goal of eradicating HIV.

Current antiretroviral (ARV) therapy is quite potent. When it works well, it completely shuts down HIV reproduction. Unfortunately, a small reservoir of infected cells remains in the body, and when people stop taking their HIV medication, the virus quickly resumes replication.

Traditional ARVs can’t target HIV genetic material (HIV DNA) inside this reservoir of infected cells. This is because the cells are inactive; most ARVs only work in cells that are actively reproducing. Researchers are now exploring drugs that either wake up these resting cells or help purge their HIV DNA and, ultimately, make the virus vulnerable to HIV drugs. These strategies are one of several being explored with the goal of eradicating HIV from the human body (see “From Mice to Men” in the October/November issue of POZ).

One hopeful new therapy is IL-7. This naturally occurring cellular messenger (cytokine) helps different types of T-cells develop, mature and reproduce. IL-7 can also cause resting CD4 cells to “wake up.” It is this latter quality that researchers are exploring in the study now under way.

The study (ERAMUNE 01)—which is being conducted by a nonprofit French institute called the Objectif Recherche VAccin Sida (ORVACS) and headed by Christine Katlama, MD, from the Hopital Pitie-Salpetriere in Paris—is enrolling people with HIV who are on a fully suppressive ARV regimen and who are judged to have a very small reservoir of infected cells based on a measurement of HIV DNA in the blood. The study will enroll 28 people living with HIV in Paris, Milian, Barcelona and London.

Katlama and her colleagues will add Isentress and Selzentry to everyone’s regimen, an approach known as treatment intensification, to help maximize control of HIV replication. Eight weeks after people add Isentress and Selzentry, the research team will give them two cycles of IL-7 injections. The primary aim is to simply decrease the size of the HIV reservoir. Secondary goals include establishing the safety of this approach and, potentially, eradicating HIV.

“The unique hypothesis tested in this study is that with [IL-7 inducing CD4 cell activation and Isentress and Selzentry containing infection of CD4s] eventually [this will contribute] to viral reservoir reduction and potential eradication,” said Thérèse Croughs, MD, the chief medical officer of Cytheris.

A similar 28-patient study, ERAMUNE 02, is being conducted in the United States—in Chicago, San Francisco and New York—and is exploring Isentress or Selzentry treatment intensification in combination with an HIV-recombinant Ad5-based vaccine to boost the immune system’s response to HIV DNA.

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Starting Antiretroviral Treatment Does Not Reduce the Incidence or Prevalence of Cervical Infection with Human Papillomavirus. 18/10/10

Starting treatment with anti-HIV drugs had no impact on the prevalence of high-risk infection

AIDSMap

By Michael Carter
18 October 2010

Starting antiretroviral treatment does not reduce the incidence or prevalence of cervical infection with human papilloma virus, US investigators report in the online journal BMC Infectious Diseases. All types of the virus persisted, including those associated with a high risk of cervical cancer.

Nor did the investigators find any evidence that better increases in CD4 cell count after starting HIV treatment increased the chances of clearing cervical infection with human papillomavirus (HPV).

Moreover, many patients who were taking HIV therapy acquired infection with high-risk strains of human papillomavirus.

“There is no immediate effect of HAART [highly active antiretroviral therapy] on HIV-infected adolescents, especially with regard to high-risk and vaccine-type HPV infection prevalence, persistence, or clearances,” comment the study’s authors. “Additionally, there is no clear pattern of HPV infection or clearance with respect to immune reconstitution (based on CD4 T-cell counts) from HAART.”

Antiretroviral therapy has been associated with remarkable improvements in the prognosis of many HIV-positive patients. Rates of AIDS-defining illnesses have fallen dramatically, including those of the HIV-related cancers Kaposi’s sarcoma and non-Hodgkin lymphoma.

Cervical cancer is also classified as an AIDS-defining cancer, and research suggests that diagnoses of this malignancy have increased since antiretroviral therapy was introduced.

Like anal cancer (rates of which have also increased), cervical cancer is associated with long-term infection with certain strains of human papillomavirus. This can cause cell changes that lead to cancer.

Information about the impact of HIV therapy on the clearance of cervical human papillomavirus is inconsistent. Some studies suggest that the immune restoration that results from antiretroviral therapy helps clear the infection, but other research has found no evidence of this.

Investigators from the US REACH (Reaching for Excellence in Adolescent Care and Health) cohort study wished to clarify this important question.

They therefore monitored the prevalence, persistence and incidence of cervical human papillomavirus infection in 373 adolescents with HIV (227) or at risk of HIV. All were aged between 12 and 19, and the HIV-infected patients acquired the infection through sex or drug use. 

These individuals were monitored for cervical human papillomavirus infection every six months, and the HIV-positive patients had their CD4 cell counts monitored at regular intervals.

The HIV-positive adolescents had a variety of antiretroviral treatment histories. A total of 100 had follow-up data before and after the initiation of HIV treatment; 57 started HIV therapy immediately they entered the cohort; and 70 never took anti-HIV drugs.

Overall, 70% of study participants had cervical human papillomavirus infection at virus, and 70% of those who were uninfected at baseline acquired the infection during follow-up.

On average the patients were followed for a little over two years.

Individuals starting HIV treatment showed good increases in their CD4 cell counts from a baseline of 471 cells/mm3 to 525 cells/mm3.

Before they started antiretroviral therapy, the HIV-positive participants had a prevalence of between 1 – 17% of infection with a high-risk type of human papillomavirus.

Prevalence in the HIV-negative individuals was between 1% -10%.

Starting treatment with anti-HIV drugs had no impact on the prevalence of high-risk infections (1 – 18%).

There was a high incidence of infections in both the HIV-positive and HIV-negative patients, with a trend for higher incidence among those with HIV.

Although CD4 cell counts increased in patients starting HIV therapy, this did not affect human papillomavirus infections and clearance patterns.

 “Overall, the results suggest that HAART has no effect on high- or possible-carcinogenic HPV infections”, comment the investigators.

For example, incidence of HPV 16 was 6.54 per 100 person years before HIV treatment was started and 6.67 per 100 person years after.

Similarly, the incidence of HPV 18 was 4.66 per 100 person years in the period before antiretroviral therapy was started and increased to 6.26 per 100 person years after patients started taking anti-HIV drugs.

Incidence of some other high-risk strains of the virus was even higher. That of HPV 53/66 was 9.83 per 100 person years in the period before HIV therapy, but was 12.80 after treatment was started.

“We observed higher prevalence and incident of possible carcinogenic…HPV types in the after HAART initiation period. Thus prevention of HPV acquisition is important, especially in vulnerable populations such as sexually active adolescents.”

The investigators acknowledge that the study’s small sample size is a potential limitation. Nevertheless they conclude that starting HIV treatment “did not show immediate effect on high-risk and vaccine type HPV incidence, clearance, and persistence

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Adding Drugs to Already Successful HIV Treatment doesn't Reduce Viral Load Further. 15/10/10

Effective combination antiretroviral therapy has dramatically reduced rates of illness and deat

15 October 2010

Intensifying effective HIV therapy with the addition of an extra drug that crosses the blood-brain barrier does not reduce residual levels of viral replication in cerebrospinal fluids or the blood, an international team of investigators report in the online edition of the Journal of Acquired Immune Deficiency Symdromes.

The researcher also found that patients continued to have evidence of immune activation and inflammation in the brain.

“Treatment intensification with a potent CNS [central nervous system]-penetrating antiretroviral drug does not reduce residual CSF [cerebrospinal fluid] HIV RNA levels or intrathecal immune activation”, write the investigators.

Effective combination antiretroviral therapy has dramatically reduced rates of illness and death in patients with HIV. Recent advancements in antiretroviral treatment mean that an undetectable viral load is a realistic goal for the vast majority of patients.

When treatment first became available in 1996 there were initially hopes that long-term suppression of HIV in the blood would eventually lead to eradication of the virus. However, it soon became apparent that HIV levels in blood were being repopulated from latent CD4 cells that were infected with the virus.

Moreover, ultrasensitive viral load tests have shown that the majority of patients taking treatment continue to have very low levels of HIV in their blood.

Residual viral load (2 to 20 copies/ml) has also been observed in the cerebrospinal fluid of individuals with undetectable blood viral loads. In addition, many patients taking HIV therapy, even if taking drugs capable of crossing the blood-brain barrier have evidence of intrathecal immune activation and inflammation.

Because of these findings, investigators wished to see if adding an extra antiretroviral drug to regimens that were already suppressing viral load would  reduce residual HIV levels in the cerebrospinal fluid and immune activation and inflammation in the brain.

Their study involved ten patients. These individuals had had an undetectable blood viral load (below 50 copies/ml) for a median of 6.5 years. Their median CD4 cell count was 465 cells/mm3, eight were men and their average age was 52.

The study lasted eight weeks. Lumbar punctures were performed on entry to the study, at baseline, after four weeks of treatment, and again at the end.  Viral load was measured in cerebrospinal fluid and markers of intrathecal immune activation and inflammation were also monitored.

Treatment was intensified by the addition of either maraviroc (Celsentri) or lopinavir/ritonavir (Kaletra), both of which have good penetration into the central nervous system, or with T-20 (enfuvirtide, Fuzeon), which does not.

During the first four weeks of the study, the patients received a brain-penetrating drug, after which they switched to T-20.

At baseline, median blood viral load was 5 copies/ml, and median viral load in cerebrospinal fluids was 2 copies/ml. Immune activation or inflammation in the brain was evident in the majority of patients.

Intensification of therapy did not further reduce residual viral load levels in cerebrospinal fluids which remained unchanged through the eight weeks of the study. Seven patients had detectable viral load in this compartment at least once. Viral load in blood was also unaffected, as were markers of intrathecal inflammation and immune activation.

Concentrations of maraviroc and Kaletra were well within their therapeutic ranges, and maraviroc was detectable in the cerebrospinal fluids of seven patients.

“We show that treatment intensification has no effect on either residual CSF HIV RNA levels or intrathecal immune activation over the course of 4 weeks with an antiretroviral drug that penetrates in the CNS”, comment the authors. “We could not detect any significant changes in the level of residual plasma viremia during the total treatment intensification period of 8 weeks.”

The investigators do not believe that their findings have any immediate implications for HIV care. Rather, they are of interest regarding “HIV persistence and reservoirs…these findings argue against the hypothesis that ongoing cycles of viral replication are the main source of residual CSF viremia and intrathecal immune [activation].”

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CASCADE Analysis Finds Antiretroviral Treatment Benefits are Evident Below CD4 Count of 500, Uncertain Above this Level. 23/7/10

Starting antiretroviral therapy with a CD4 cell count between 350 and 500 cells/mm3 reduces the likelihood of HIV disease progression

AIDSMap

By Liz Highleyman
23 July 2010

Starting antiretroviral therapy with a CD4 cell count between 350 and 500 cells/mm3 reduces the likelihood of HIV disease progression and death relative to initiation below 350 cells/mm3, according to findings from the large CASCADE study presented on Thursday at the Eighteenth International AIDS Conference in Vienna. Starting treatment with more than 500 cells/mm3 did not appear to confer additional benefit, but this analysis did not take into account non-AIDS-related conditions.

Numerous randomised trials have demonstrated the benefits of starting antiretroviral treatment before significant immune system damage occurs; that is, before the CD4 cell count falls much below 350 cells/mm3 and certainly before it hits 200 cells/mm3.

The benefits and risks of starting treatment above 350 cells/mm3 are less clear. Randomised trials to address this question are underway, but in the meantime a growing body of data from observational studies suggests starting earlier may lead to better outcomes, particularly with regard to non-AIDS-related conditions such as cardiovascular disease. Ongoing immune activation and chronic inflammation due to low-level HIV may contribute to problems throughout the body even while CD4 cell count remains high, some experts believe.

Joseph Eron from the University of North Carolina presented the latest findings from CASCADE, a collaborative natural history study of HIV seroconverters from more than two dozen clinical cohorts in Europe, Australia and Canada, followed since the advent of highly active antiretroviral therapy, or HAART.

The 9455 participants in the CASCADE 'When to Start' analysis were enrolled between January 1996 and May 2009. At the time of enrolment they were at least six months past seroconversion, free of AIDS and had not yet started antiretroviral therapy.

Just over three-quarters were men and a majority (56%) were gay/bisexual. The average age at the time of seroconversion was 30 years and the estimated duration of infection was 1.3 years.

Participants were analysed as 161 sequential nested cohorts of people enrolled during one month. The researchers measured time between the end of the prior month and the occurrence of an AIDS-defining illness or death. Participants who remained alive could join the next monthly cohort, so some individuals were members of multiple cohorts.

Researchers recorded whether participants started HAART (defined as any three-drug antiretroviral regimen) and collected information about demographic and disease-related factors including sex, age, history of injecting drug use, hepatitis B or C co-infection, CD4 cell count and HIV viral load. Eron described the study as "intent-to-treat in spirit".

Participants were divided into five categories according to CD4 cell count: 0 to 49, 50 to 199, 200 to 349, 350 to 499 and 500 to 799 cells/mm3. Only 183 people fell into the lowest category, whilst the three highest categories each had more than 4000 participants. The researchers did not include people with more than 800 cells/mm3 because there were too few events for a statistically meaningful analysis.

Participants were followed for nearly five years on average, contributing a total 52,268 person-years of data. Overall, 812 people (8.6%) progressed to AIDS during the study period and 544 participants (5.8%) died.

Importantly, the analysis did not include occurrence of non-AIDS-defining conditions of the type reported more frequently in HIV-positive people with well-preserved immune function, for example heart, liver and kidney disease. Eron said the causes of death in this analysis were unknown, though presumably recorded by investigators for the specific cohorts.

Being an observational study, outcomes amongst people who started therapy and those who deferred treatment cannot be directly compared since participants were not randomly assigned to one strategy or the other.

On the whole, people who started treatment had better prognosis in some respects (including being less likely to have a history of injecting drug use or to be co-infected with hepatitis B or C) but poorer prognosis in others (including higher viral load and a slightly lower CD4 cell count on average).

The benefits of starting treatment were clear in the three lower CD4 count categories. Amongst people with 0 to 49 cells/mm3, for example, the rate of AIDS or death was 55 per 1000 person-years for those who started treatment, compared with 193 per 1000 person-years for those who deferred treatment, or about a 70% risk reduction. In the 200 to 349 cells/mm3 group, the rates were 19 per 1000 person-years for those who started and 29 per 1000 person-years for those who waited, about a 40% reduction.

The advantages of treatment initiation were less evident in the two higher CD4 count groups. The rate of AIDS or death in the 350 to 499 cells/mm3 category rose from 17 per 1000 person-years for those who started to 21 per 1000 person-years for those who deferred, a 25% reduction after adjusting for other factors.

In the 500 to 799 cells/mm3 category, AIDS or death rates were 15 and 19 per 1000 person-years for starters and deferrers, respectively – essentially no change in risk in the adjusted analysis. These patterns were similar overall when looking at death alone.

The researchers calculated that they would have to treat only three people with 0 to 49 cells/mm3 to prevent one case of progression to AIDS or death within three years. The number needed to treat rose to 21 for the 200 to 349 cells/mm3 category and to 34 for the 350 to 499 cells/mm3 category.

They were unable to calculate a figure for AIDS or death in the 500 to 799 cells/mm3 category but, looking at death alone, they determined that 239 people would have to start treatment in order to prevent a single death.

The researchers concluded that starting antiretroviral therapy with a CD4 count below 500 cells/mm3 "appears to reduce risk compared to deferring at baseline". However, at CD4 counts of 500 to 799 cells/mm3, there was "no apparent benefit to [treatment] initiation for the larger population of patients with CD4s in this range".

These findings support current US treatment guidelines recommending initiation of therapy when CD4 cell count falls below 500 cells/mm3 and suggests that the World Health Organization's threshold of 350 cells/mm3 may be too low. 

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5.2 Million Now on ART — and More to Come; WHO Officially Releases 2010 HIV Treatment Guidelines. 20/7/10

World Health Organisation (WHO) formally launched the 2010 guidelines

AIDSMap

20 July
By Theo Smart

Proclaiming that at least 5.2 million people with HIV were now receiving antiretroviral therapy (ART) in low and middle-income countries, the World Health Organisation (WHO) formally launched the 2010 guidelines on Antiretroviral therapy for HIV infection in adults and adolescents, during a press conference at AIDS2010 in Vienna.

The guidance, with its emphasis on earlier treatment, will dramatically increase the number of people with HIV who qualify for treatment, from an estimated 10 million to an estimated 15 million. WHO assembled a panel of experts to discuss what these guidelines will mean, how acceptable they are to the community and what will it take to implement them.

“Earlier treatment” [will translate] to longer lives, healthier lives, and fewer infections,” said Dr Gottfried Hirnschall, WHO Director of HIV/AIDS.  Though recommending earlier treatment has been criticized by some who say it will be too increase costs to programmes at a point when the recession is threatening the dream of universal access, Dr Hirnschall said “we have enough evidence that these investments will however play out in a positive sense with health cost savings in a few years, and we really think we are in a win-win situation.”

WHO got the roll-out rolling

WHO has long argued that ART could be efficiently delivered to millions of people living with HIV in resource-limited settings by using a public health approach. In 2003, WHO launched the historic “3 by 5” initiative to provide access to HIV treatment to 3 million people living in low- and middle-income countries by the end of 2005. WHO’s approach to scaling up treatment has generally been simpler and more cost-conscious than many of ART programmes that were subsequently implemented.

The 3x5 goal wasn’t quite reached, but it was important to set the target.

“When we started the 3X5 initiative in 2003, many people were sceptical, but now we have put 5.2 million people on treatment,” said Dr Hiroki Nakatani, WHO Assistant Director-General for HIV, Tuberculosis, Malaria and Neglected Tropical Diseases who opened the press conference. Indeed, since 2003, the number of people receiving HIV treatment has increased 12-fold. “The additional 1.2 million were gained in 2009, which is the largest increase in people accessing treatment in a single year.”

The new guidelines

The new guidance, which had an advance-release towards the end of last year, contains four key changes.

-It promotes earlier treatment, recommending starting HIV treatment at 350 cells or below.
-It recommends moving to more patient-friendly and less toxic regimens, phasing out stavudine (d4T), which is more toxic than initially thought
-It recommends starting coinfected people with TB (or hepatitis B if it requires treatment) on ART earlier, regardless of the CD4 count
-It acknowledges the prevention benefits of treatment.

“The big additional benefit is the prevention benefit of scaling up treatment. In a way we are stating the obvious, that somebody who is on treatment who has less virus is less infectious and less likely to transmit the virus. But now we have sufficient scientific evidence so that we can formally incorporate this into the recommendation,” said Dr Hirnschall.

“We believe that with this reduction of mortality of up to 20% in the next five years, important reductions in TB related mortality as well, and the additional prevention benefit, this is quite a revolution,” Dr Hirnschall added.

According to Dr Kevin Moody of the Global Network of People Living with HIV/AIDS (GNP+), the guidelines are welcomed by people living with HIV around the world

“We think it will help to improve people’s quality of life, and people will have better health outcomes. We are also interested in the fact that earlier treatment may have prevention benefits,” he said.

Notably, WHO consulted extensively with communities of people living with HIV in different parts of the world before drafting the guidelines.

“HIV positive people are mothers, fathers and children. We aren’t a special group demanding special treatment. All we want is our right to health, which includes the right to treatment,” he added.

Kenya quick to adopt new guidelines

However, it will be up to the countries whether or not to implement the guidelines — and there will be some challenges putting them into operation on the ground.  But said Dr Peter Cherutich of the Kenyan National AIDS & STI Control Programme, these challenges are not insurmountable.

“Implementing these guidelines at country level is not necessarily going to be easy, but we see this as a challenge not a barrier. These are challenges we can find solutions to,” he said. “These guidelines are feasible in Africa, and we in Kenya will try to provide leadership demonstrating this.”

Kenya has about 1.4 million people with HIV infection. About 350,000 qualified for treatment under the old guidelines, and this has now increased to 600,000. But the prevention benefits of treatment have been a powerful incentive to the programme.

“Our overriding goal in adopting this is that our HIV incidence is too high, and so we are adopting these guidelines in part to reduce transmission of HIV,” said Cherutich.

However in order to reap the prevention benefits of treatment, it will be necessary to identify the people who need treatment.

“With these new guidelines the paradigm of testing has to shift to identify people earlier in infection,” said Cherutich.

The country has implemented provider-initiated testing and counselling, and has also done pioneering work demonstrating high rates of acceptance of door-to-door testing of the general population, and targeted testing of the partners and other family members of people living with HIV.

“We’ve expanded efforts, including testing in the home and testing couples. We need to move to more proactive, human rights based, provider-initiated testing. We’ve seen it is possible and it is happening in Kenya where more than half now know HIV status,” he said.

“It’s important that people know their status,” said Dr Moody. “We also hope that through promotion of the guidelines, people will be more likely to get tested.”

He also believes that the community of people living with HIV need to be more involved in testing campaigns working in collaboration with the formal health sector, for example by training people with HIV to test and counsel others.

Concerns about resistance, increased sexual risk taking behaviour, and costs

Some audience members posed questions to the panel about whether earlier treatment (and the notion that it might work as prevention) could have some negative consequences, including an increase in resistance, disinhibition of sexual risk taking behaviour, and significant and unsustainable costs to health systems at a time of global recession.

“We are working with about 15 countries on resistance in RLS, but in most countries, the development of resistance has been less than expected, less than 5%,” said Dr Hirnschall. “In the south, people said that there wouldn’t be enough support for adherence, but the experience has been otherwise.”

“Adherence rates in Africa are comparable to the rest of the world,” agreed Dr Cherutich. “We need to use the resources we’ve developing of counselling people to take their treatment, adherence support. But we also need to plan a process for breakthroughs, and have a surveillance program for resistance in place.”

 “Pretty much the only risk is that people don’t take the drugs regularly. Side effects are one of the reasons for this, but these guidelines switch to less toxic drugs and so should help with adherence,” said Dr Bernard Schwartlander, Director, Evidence, Strategy and Results, UNAIDS.

The biggest question in everyone’s minds was how to pay for putting more people on sometimes more expensive treatment. Looking at the annual cost over the next five years, the additional cost will be US$2 billion. Clearly this issue had Dr Cherutich concerned.

“Of course, the issue of cost is big challenge to us,” he said that Kenya has been contributing a minimum level which has gone up from US$ 7 to 13 million. “But that’s a drop in bucket of what is needed, so we need partnerships… We’ve been looking at the private sector, and we have an expectation that PEPFAR and the Global Fund will help us meet our commitments.

Dr Schwartlander stressed that the increased upfront costs would be offset by savings over time.

"The investments we make today can not only save millions of lives but millions of dollars tomorrow,” said Dr Bernhard Schwartlander, Director, Evidence, Strategy and Results, UNAIDS. " But the big problem is that people have been coming forward too late, and treating people who are very sick is very costly."

Treating people earlier would prevent the eventual costs of hospital care. In addition, he said that much of the cost of treatment actually comes from treatment delivery monitoring, which may be offset somewhat by using safer drugs. Finally, prevent more infections “will have huge returns, which will return on our investment as we move forward,” he said.

“We shouldn’t exaggerate or overestimate what the additional costs are,” said Dr Hirnschall. He pointed out that the new guidelines essentially means that an HIV-positive person, who will probably be on treatment for up to 30 years, will only go onto treatment two year earlier.

Even so, Dr Moody pointed out that the guidelines have come at an alarming time when funders are cutting back support, the G8 has broken their promises, and it is difficult to get funding even to meet old guidelines. Nevertheless, he stressed that people living with HIV, are committed to advocate that countries meet their funding commitments.

“We need to continue to make the case and sustain commitment to universal access and say it loud and clear,” said Dr Hirnschall. But in addition, programmes do have to look at how they operate, and make strategic linkages and use resources more efficiency (including the community).

“We have to look at what we have and try to use in optimal way.  We still need to find ways to simplify what we are doing now and to reduce costs. For example, there’s no way that we can accept that second line drugs still cost what they cost,” he said.

Moving forward, he said WHO would work very closely with countries to try to identify operational bottlenecks, and funding gaps along the way. But “double standards regarding treatment should not exist between north and south… these guidelines should be applicable in any part of the world,” he said.

Ultimately, the question of cost should not be what dictates WHO policy, according to Dr Nakatani. 

“Guidelines should be evidence-based, and should be applicable to anyone rich or poor,” he said in closing.

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5.25 Million Receiving ARVs by End of 2009. 28/9/10

The global target of universal access to HIV treatment by 2010 has not been met

AIDSMap

By Keith Alcorn
28 September 2010

The global target of universal access to HIV treatment by 2010 has not been met, United Nations agencies reported today, but more than half of the people in most urgent need of treatment were already receiving it by the end of 2009.

Over 1.2 million started treatment in 2009, the largest increase in a single year since antiretroviral drugs became available in low and middle-income countries in the early 2000s. Just over 1 million of those starting treatment lived in sub-Saharan Africa.

The 2010 progress report Towards Universal Access was released today by three UN agencies, the World Health Organization, UNAIDS and UNICEF, with a warning that new WHO treatment guidelines mean that only one-third of people in need of treatment are currently getting it.

The gap between the numbers treated and the target has widened because of a change in WHO treatment recommendations to endorse earlier treatment.

In 2010 WHO recommended that the threshold for starting antiretroviral treatment should rise from 200 cells to 350 cells/mm3.

The impact of the 2010 revision of WHO treatment guidelines has been to boost the number of people in need of HIV treatment from 10.1 million to 14.6 million. Of these, 10.6 million live in sub-Saharan Africa.

According to the definitions used in the previous WHO guidelines 52% of people in need of treatment were receiving it by the end of 2009, at a time when these guidelines were still the model for all but 29 countries worldwide.

Under the new eligibility criteria, coverage is estimated at around 36%. Coverage is lowest in Eastern Europe and Central Asia (19%)  and North Africa and the Middle East (11%) and highest in Latin America (51%).

Two-thirds of countries had introduced policies supporting provider-initiated testing and counselling by the end of 2009, and 67 million people took an HIV test in 2009. The numbers of tests performed is estimated to have grown by 22% in 2009.

However, population-based surveys in ten African countries show that only 40% of people with HIV know their HIV status.

Women were more likely to know their HIV status than men. In eastern and southern Africa half of all pregnant women received an HIV test in 2009, compared with 26% worldwide.

Half of pregnant women testing positive were reported to have  been assessed for eligibility to receive antiretroviral drugs for their own health, and overall, 53% of pregnant women with HIV received antiretrovirals to reduce the risk of mother-to-child transmission (compared with 45% in 2008).

Thirty-five per cent of infants born to mothers with HIV received antiretroviral prophylaxis in 2009, but only 15% of infants received an HIV test within two months of delivery, underlining major deficiencies in infant HIV diagnosis and treatment. WHO now recommends that children infected with HIV should begin treatment in the first year of life.

The number of children receiving antiretroviral therapy rose by 29% in 2009, to around 350,000.

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A Slower Response to HIV Treatment is Just as Good as a Fast Response. 15/6/10

People whose HIV levels drop more slowly after starting antiretroviral (ARV) therapy do just as well over two years as people whose virus drops rapidly

15 June 2010

People whose HIV levels drop more slowly after starting antiretroviral (ARV) therapy do just as well over two years as people whose virus drops rapidly, according to a research letter published in the June 19 issue of AIDS. These data potentially refute a long-standing theory that viral loads should decrease quickly during the initial months of treatment to maximize the chances of long-term success on a particular drug regimen.

In recent years, several studies have shown that some ARVs—especially Isentress (raltegravir)—are able to reduce HIV levels more rapidly than other drugs. Generally, experts define a rapid response as achieving a viral load of less than 50 copies within the first 12 weeks after starting treatment, and a slow response as achieving an undetectable viral load 12 to 24 weeks after starting treatment.

Theoretically, some researchers believe, a rapid response to treatment confers more benefits than a slower response, such as a greater likelihood of keeping viral load undetectable for a prolonged period of time. However, this hasn’t been proved.

To explore this hypothesis, Graham Moyle, MD, from Chelsea and Westminster Hospital in London, and his colleagues analyzed data from two studies—ARTEMIS and TITAN.  Both studies involved people who were new to HIV treatment, and both compared Norvir (ritonavir)–boosted Prezista (darunavir) with Kaletra (lopinavir plus ritonavir).

Moyle and his colleagues found that people who had a slower virological response to treatment were no less likely to have an undetectable viral load 96 weeks after starting treatment than those who had a rapid response.

Moyle’s team did, however, find that a person’s pre-treatment viral load was associated with long-term treatment efficacy. Those with very high pre-treatment viral loads—though not defined by the authors, high baseline viral loads are generally those over 100,000—were more likely than those with lower virus levels to have their virus rebound with 96 weeks of starting treatment.

In the ARTEMIS study, people taking Kaletra were also more likely to have virus levels reemerge by 96 weeks than people taking Prezista.

The authors found that the results from TITAN and ARTEMIS are consistent with several other studies. In AIDS Clinical Trials Group (ACTG) 5142, people taking a Sustiva (efavirenz)-based regimen saw their viral loads drop more quickly than those taking a Kaletra-based regimen. After 96 weeks, however, people taking Kaletra were less likely to have developed drug resistance if they had treatment failure than those taking Sustiva.

Likewise, a study comparing Isentress with Sustiva found that similar proportions of those on both drugs maintained virus levels under 50 copies during the course of the study, despite the fact that people taking Isentress saw their viral loads plummet faster in the first weeks after initiating treatment.

The same dynamic appears to be true for people who are treatment experienced. The DUET study compared Intelence (etravirine)—plus an optimized background regimen of other drugs—with a placebo plus an optimized background regimen. In this study, as with the others, a quicker drop in virus levels did not predict long-term treatment success.

This recent emphasis on achieving a rapid response to treatment has likely caused at least some people to feel anxious if they took longer to reach undetectable after starting a new regimen. According to the authors, that anxiety might be groundless. They conclude: “These results from the ARTEMIS and TITAN trials show that the speed of initial suppression of HIV RNA in the first 24 weeks of antiretroviral treatment does not reliably predict whether patients will show long-term suppression at week 96.”

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AFRICA: Prompt Start to ART Essential – Studies. 19/2/10

Studies from South Africa, Uganda and Zimbabwe presented at the 17th Conference on Retroviruses and Opportunistic Infections in San Francisco (ending 19 February), all found late enrolment of patients on life-prolonging antiretroviral treatment (ART) to be a significant barrier to treatment programmes.

irinnews

NAIROBI. Many HIV-positive African patients are starting treatment too late for it to be effective, new scientific studies have shown.

Studies from South Africa, Uganda and Zimbabwe presented at the 17th Conference on Retroviruses and Opportunistic Infections in San Francisco (ending 19 February), all found late enrolment of patients on life-prolonging antiretroviral treatment (ART) to be a significant barrier to treatment programmes.

"Over each calendar year, we see increasing numbers of patients [enter] the programme," Suzanne Ingle, from the University of Bristol in the UK, who co-authored a study on pre-treatment mortality in South Africa's Free State Province, said via webcast. "However, there are still many deaths that occur in the period while waiting to start treatment; these deaths are most likely to occur in the most immuno-suppressed patients."

Patients with stronger immune systems - measured by a higher number of CD4 cells per cubic millilitre of blood - were not monitored frequently enough to enrol them for treatment at the correct time, Ingle said.

During the study, almost 3,000 of 22,000 participants had CD4 counts better than 250 - the then nationally stipulated threshold - and so did not start treatment immediately.

"The median time to their next CD4 measure was six months; however, within this time patients had experienced a median CD4 cell decline of 113," Ingle added. "By the time these patients were assessed again, a large proportion of them would have dropped to well below the treatment eligibility threshold."

Patients with CD4 counts below 200 are at high risk of opportunistic infections. The World Health Organization (WHO) recently reviewed its treatment guidelines to recommend that treatment start sooner, at a CD4 level of 350.

Ingle noted that "loss to follow-up" - where patients starting HIV care turn up for a first visit and are not seen again - was also a significant problem.

Late enrolment, poorer results

Presenting findings from a Development of Anti-Retroviral Therapy (DART) in Africa trial in Uganda and Zimbabwe, Paula Manderi from the Uganda Virus Research Institute said patients starting treatment with very low CD counts were unable to see their immune counts recover to levels above 250.

"If a patient still had a CD4 count of below 50 cells after a year of treatment, there is only a 9 percent chance that they would ever attain 250 cells," she said via web cast.

A CD4 cell count of below 125 after a year of treatment was identified as the cut-off point at which patients were unlikely to reach 250.

"Our data highlights the importance of expanded earlier diagnosis and earlier initiation of treatment at higher CD4 counts," Manderi said.

Ingle suggested that pre-ART mortality could be reduced by fast-tracking the most immune-deficient patients, raising the treatment eligibility guidelines in line with the new WHO recommendations, and improving monitoring and retention of patients not yet eligible for ART.

According to the WHO, almost three million people in sub-Saharan Africa are enrolled in ART programmes, which represents 44 percent of people who need treatment.

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AIDS 2010: Number of HIV-Positive Patients on ARVs Grew to 5.2M In 2009 with 10M Still in Need, WHO Says. 20/7/10

Number of HIV-positive people receiving ARVs for their infections jumped by more than a quarter in 2009,

20 July 2010

"The number of HIV-positive people receiving antiretroviral drugs [ARVs] for their infections jumped by more than a quarter in 2009, growing from 4 million to 5.2 million, the World Health Organization said Monday at the International AIDS Conference in Vienna," the Los Angeles Times reports (7/19).

"Between 2003 and 2010, the number of patients receiving lifesaving antiretroviral treatment increased twelve-fold, according to the Geneva-based body," the Associated Press notes (Oleksyn, 7/19).

"This is the largest increase in people accessing treatment in a single year. It is an extremely encouraging development," Hiroki Nakatani, WHO assistant director-general for HIV, tuberculosis, malaria and neglected tropical diseases, said in a statement issued by the WHO (7/19).

The WHO in November revised its HIV treatment recommendations, advising HIV treatment begin when the patient CD4 levels – a measure of immune system response – fall around 350, rather than 200  (Kaiser Daily Global Health Policy Report, 11/30). During AIDS 2010, the WHO will be calling for countries to begin earlier HIV treatment for patients living with HIV, "stating that early use of medicines also acts as a preventive measure by reducing levels of the virus in the body, so carriers are less likely to pass on the disease," as well as helping slash rates of HIV-related deaths, Bloomberg reports (Craig, 7/19).

On Monday at AIDS 2010 the WHO "issued the first overhaul of its guidelines on HIV drugs in four years," Agence-France Presse reports. In the 156-page report the WHO elaborated on the HIV treatment recommendations the agency issued last November, "along with many other guidelines on drug use, including second-line therapy if a first course of treatment fails," the news service writes.

"Guideline revisions have an enormous impact, both for new patients and health budgets," AFP writes. "Earlier initiation means that people will be exposed longer – about one or two years more, said the report – to ART's side effects and the risk of viral resistance." According to the WHO, the report will be updated again in 2012, AFP notes (7/19).

"WHO's treatment guidelines expand the number of people recommended for HIV treatment from an estimated 10 million to an estimated 15 million. The cost needed for HIV treatment in 2010 will be about US$ 9 billion, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS)," according to the WHO statement.

"Starting treatment earlier gives us an opportunity to enable people living with HIV to stay healthier and live longer," Gottfried Hirnschall, WHO director of HIV/AIDS, said (7/19).

"Earlier HIV treatment can prevent so-called 'opportunistic infections' including tuberculosis (TB), which is the biggest killer of people with HIV," Reuters reports (Kelland, 7/19). "The agency estimated that AIDS-related deaths could be reduced by 20% from 2010 to 2015 if the new recommendation was widely adopted. Tuberculosis deaths ... could be reduced by as much as 90% if people with both HIV and TB infections began treatment earlier," according to the Los Angeles Times (7/19).

TV Shows Help Change Attitudes About HIV/AIDS

A study of MTV shows in Kenya, Trinidad and Tobago and Zambia designed to convey messages to young people about HIV/AIDS had "dramatic" results on attitudes about the disease, Reuters reports. Researchers found that the U.N.-backed shows changed the way young people think about HIV/AIDS, according to the study, released Tuesday at AIDS 2010, the news service writes (Kelland, 7/20).

"UNICEF and PEPFAR worked out priority messages to get across to young people through the story, about having multiple sexual partners, about the need to get tested for HIV, and about stigma," the Guardian writes (Boseley, 7/20).

"MTV, with funding from the Bill & Melinda Gates Foundation, commissioned Johns Hopkins University to evaluate" the drama series, which reached youth in 96% of the Top 50 HIV/AIDS impacted countries working with over 85 broadcasters in over 100 countries," according to a press release. The study "shows that young people understand the messages conveyed in [the TV series] Shuga, that young people talk about HIV issues after seeing the programme. Among those young people who have seen the programme, those who like and find the storylines realistic are more likely to change their attitudes and behavioural intentions around HIV and AIDS (towards healthier attitudes and behaviours)," the press release states (7/20).

"More than 80 percent of those who saw Shuga believed it changed their thinking about multiple concurrent partners, HIV testing and the stigma associated with" HIV, Reuters writes (7/20).

News Outlets Examine Search For AIDS Vaccine

"AIDS experts and advocates gathering in Vienna … will hear about progress in protecting people from the deadly virus using drugs, and ways to affect behavior. No breakthrough news is expected on a vaccine. But researchers are more hopeful than they have been in years that it may be possible," Reuters reports in an article highlighting recent progress towards and AIDS vaccine.

"Two studies published in the past year have greatly raised hopes," the news service writes. "In one published last September, a combination of two older vaccines lowered the infection rate by about a third after three years among 16,000 ordinary Thai volunteers. In a second study, published earlier this month, researchers discovered human antibodies that can protect against a wide range of AIDS viruses."

"There has been a renaissance in AIDS vaccines," Seth Berkley, president of the International AIDS Vaccine Initiative, said (Fox, 7/17). A related Reuters factbox notes some recent AIDS vaccine developments (7/18).

"Experts are optimistic that breakthroughs in HIV vaccine research are possible if they work together," Inter Press Service writes in an article examining the quest to create an effective AIDS vaccine. According to IPS, the Global HIV Vaccine Enterprise, a collaborative group comprised of more than 400 scientists from around the world, plans to release a strategic plan in September. The article also discusses other prevention approaches and outlines why a vaccine is so desirable (Jaffer, 7/18).

Group Wants Investigation Of U.S. Trade Policy's Affect On Drug Access; PEPFAR Saves With Generics

A coalition of health and HIV/AIDS organizations announced Tuesday that they had "formally asked" U.N. Special Rapporteur on the Right to Health Anand Grover to examine whether U.S. trade policies are "violating the health rights of millions of poor people around the world" because they can make it harder to access "life-saving drugs," Reuters reports.

According to the groups, the U.S. has used an "annual report produced by the U.S. Trade Representative's office that ranks countries with the worst records on protecting U.S. intellectual property rights for goods ranging from CDs to medicines … to pressure countries to give up certain public health rights they have under a World Trade Organization agreement on intellectual property rights known as TRIPS."

"'Up to and including the 2009 Special 301 report, Brazil, India, Thailand and other countries were threatened with sanctions under Special 301 for taking advantage of TRIPS flexibilities, including utilizing transition periods and issuing compulsory licenses' to allow domestic firms to produce cheaper versions of drugs patented by U.S. companies, the groups said in their allegation letter to Grover," Reuters writes. "This year's Special 301 report again put Thailand on its 'priority watch list,' one step short of its most serious designation. The country has battled with U.S. drug companies over steps it has taken in its aggressive anti-AIDS campaign" (Palmer, 7/20).

In related news, a study published in the Journal of the American Medical Association shows that PEPFAR "saved an estimated $323,343,256 from 2005 to 2008 through the use of generic antiretroviral drugs (ARVs)," according to a press release issued by PEPFAR, Georgetown University's O'Neill Institute and Supply Chain Management System.

"Among PEPFAR-supported programs in 16 countries, availability of generic ARVs was associated with increased ARV procurement and substantial estimated cost savings. While ARV expenditures increased from $116.8 million in 2005 to $202.2 million in 2008, procurement increased from 6.2 million to 22.1 million monthly packs. The proportion spent on generic ARVs increased from 9.2% in 2005 to 76.4% in 2008, and the proportion of generic packs procured increased from 14.8% in 2005 to 89.3% in 2008," the press release states.

Ambassador Eric Goosby, the U.S. global AIDS coordinator, said, "Drugs are no longer the main driver of treatment costs, so in addition to savings from generics, the systems we've put into place for procurement and distribution are making efficiencies possible throughout national health systems. Our increasing efficiency is saving money that PEPFAR and the broader U.S. Global Health Initiative can use to save more lives – and that's the bottom line" (7/18).

All of the Kaiser Family Foundation's webcasts of select sessions from AIDS 2010 are available here

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Adherence Partners Give Short-Term Boost, But No Long-Term Benefit, in Nigerian Study. 26/1/10

In contrast to other studies the authors found that living closer to the clinic was associated with better adherence and virological outcomes.

Carole Leach-Lemens

People with HIV who selected treatment partners to support their adherence were more likely to return to the clinic to collect further doses of antiretrovirals, and showed a higher rate of viral suppression after six months of treatment, but showed no longer-lasting advantage in terms of viral suppression, CD4 cell counts or mortality, Nigerian and American researchers report in the Journal of Acquired Immune Deficiency Syndromes.

In contrast to other studies the authors found that living closer to the clinic was associated with better adherence and virological outcomes. They suggest this may be an argument in support of decentralisation of HIV services in resource-poor settings, but say that they are unable to establish a causal association, and suggest further study.

Adherence is vital to successful antiretroviral treatment. Drug resistance and treatment failure are associated with non-adherence.

While there are high rates of adherence in resource-poor settings, there is always a need to develop improved adherence strategies for better health outcomes.

Health care workers and volunteers play an important role in ensuring adherence. Disclosure of HIV status is central to this, and is independently associated with the prevention of virologic failure. However, concern over confidentiality as well as the sustainability of such an approach led the authors to look at the little studied role of pre-existing social networks, in particular patient-selected treatment partners, on health outcomes.

Over a period of 18 months (June 2006-December 2007) 499 HIV-infected treatment naïve adults (over 15 years of age) attending the Jos University Teaching Hospital (JUTH) ART clinic in Nigeria were randomised to standard-of-care (SOC) or patient-selected treatment partner-assisted therapy (TPA).

Each patient was followed for 48 weeks. Outcomes studied included virologic control (viral load reduction of greater than 1 log at week 12 and viral load below 400 copies at weeks 24 and 48), adherence to drug pick-up, CD4 cell counts and mortality.

All antiretroviral drugs were given out at the clinic pharmacy. Before starting ART all patients took part in a two-hour interactive adherence education session. Led by openly HIV-infected registered nurses trained in HIV adherence counselling, the sessions, conducted in the local language (Hausa) as well as English, took place in a dedicated room in the clinic.

At each drug pick-up visit (28 days) the study pharmacist, unaware of the treatment arm, gave further support as well as targeted information related to self-reports of adherence and side effects. The study pharmacists are trained in adherence counselling and have a minimum of three years experience at the JUTH ART clinic. Patients at 24 weeks with a viral load above 400 copies/ml had intensive adherence re-training.

Those assigned to the TPA arm received the interventions previously described (the standard of care) and chose a treatment partner aware of the patient’s status and who lived in the same house or very close by. TPAs attended one adherence education session. TPAs received no compensation but received travel allowances if needed. They were asked to watch participants taking their drugs at least once a day, help with reporting of, and management of side effects, as well as reminding participants when it was time to pick up drugs.

At week 24 more participants with TPAs had viral suppression compared to those with SOC alone ( 61.7% versus 50.2% (odds ratios (OR)=1.58, 95% CI 1.11 to 2.226, p<0.05). However at week 48 there was no significant difference in viral load suppression (65.3% (TPA) compared to 59.4% (SOC) OR=3.06, 95% CI:0.89 to 1.84. p>0.05). There was no significant difference in CD4 count or mortality rate in either arm at week 48.

The authors suggest that the absence of a long-term impact of TPAs on viral suppression is explained by the fact that all patients who had a viral load above 400 copies/ml at week 24 received focused adherence retraining. However the authors refer to another randomised study that also found no long-term virologic benefit with treatment partners.

Other explanations they note include the possibility that even a relatively low level of adherence (>54%) may be sufficient to ensure viral suppression with an NNRTI-based regimen. As a consequence, modest increases in longer-term adherence in the TPA group may not result in a superior virologic outcomes in the TPA group.

The high level of adherence seen in both arms is consistent with previous studies in sub-Saharan Africa, note the authors.

The TPA arm were three times more likely to demonstrate 95% adherence as measured by drug pick-up rates at week 24 (89% versus 72% in the SOC group, OR = 3.06. 95% CI: 1.89-4.94, P<0.01), and twice as likely to demonstrate 95% adherence at week 48 (80% versus 67% for the SOC arm, OR=1.95. 95% CI: 1.29-2.93, P<0.01).

The authors note, as have other investigators, a disparity between drug pick-up rates and virologic suppression when using pharmacy records as a measure.

They stress drug pick-up adherence does not mean that patients will take the drugs as prescribed, highlighting the limitation of drug pick-up as a measure of adherence. The authors note while this is the first randomised study to show a link between improved drug pick-up adherence and treatment partner-associated therapy, it did not show lasting virologic, immunologic or mortality benefits.

They suggest their findings point to the importance of looking at non-adherence endpoints in the evaluation of adherence interventions and to the evaluation of interventions not focused on drug pick-up alone but which include the taking of the drug.

The authors conclude that since improved drug pick-up adherence is associated with the use of patient-selected treatment partners but not on lasting viral suppression, CD4 count increase or mortality, strategies are needed to adapt improved drug pick-up adherence that will result in lasting changes to health outcomes.

Referente

Babafemi, O Taiwo et al. Assessing the virologic and adherence benefits of patient-selected HIV treatment partners in a resource-limited setting. J Acquire Immune Defic Syndr Vol (advance online publication), 2009.

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Africa: Extra 1.2 Million People Able to Gain Access to Antiretroviral Drugs, Says UN Health Agency. 19/7/10

WHO has goal of eventually expanding the number of cared-for to 15 million.

19 July 2010

The World Health Organisation said at a conference in Vienna that the largest yearly increase in the number of people able to gain access to antiretroviral drugs was an "extremely encouraging development".

Official figures show that an extra 1.2 million people were able to obtain medication to repress the virus that causes Aids bringing the total figure to 5.2 million.

The WHO issued new recommendations on Monday for earlier treatment of people with HIV, with the goal of eventually expanding the number of cared-for to 15 million.

Antiretroviral therapy is a combination of powerful drugs that prevent the human immunodeficiency virus [HIV] from replicating in immune cells. Administered at a key stage of infection, it can reduce the virus to negligible levels, allowing the patient to live an almost

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Africa: A Radical New UNAIDS Treatment Strategy. 16/7/10

UNAIDS has launched a simpler, more cost-effective approach to HIV treatment

AllAfrica

16 July 2010

Johannesburg — UNAIDS has launched a simpler, more cost-effective approach to HIV treatment, aimed at simultaneously achieving two holy grails of the AIDS response: drastic reductions in AIDS-related deaths and new HIV infections.

The approach, dubbed "Treatment 2.0", aims to drastically scale up testing and treatment using current best practices and future innovations in antiretroviral (ARV) drugs and diagnostics. The prevention benefits of extending treatment to all those in need of it are based on mounting evidence that people on ARV treatment are much less likely to transmit the virus.

UNAIDS estimates that successful implementation of Treatment 2.0 could avert 10 million deaths by 2025, and reduce new infections by one-third.

A report on the new strategy has been released ahead of the International AIDS Conference, starting on 18 July in Vienna, where one of the hot topics will be why most countries will fail to meet the goals of universal access to HIV prevention, treatment and care by the December 2010 deadline.

Worrying indications that international financial support for the AIDS response is flagging will also be debated, but UNAIDS director Michel Sidibe is pitching the Treatment 2.0 approach as offering a potential solution to both concerns.

"For countries to reach their universal access targets and commitments, we must reshape the AIDS response," he said in a statement. "Through innovation we can bring down costs, so investments can reach more people."

Better drugs

Treatment 2.0 calls for the creation of "better" HIV drugs that would be less toxic, combine multiple ARVs into one pill, and be more tolerant of treatment interruptions, as well as quicker and cheaper diagnostic tools.

The current generation of ARVs have far fewer side effects than those of a decade ago, and some are available in fixed-dose combinations, but poor adherence quickly leads to the development of drug resistance and the need to switch to more expensive second-line medicines.

Second-line ARVs also incur a number of non-drug related costs, like laboratory monitoring and clinic visits, which are often enough to push treatment out of reach, but Treatment 2.0 urges all involved in fighting HIV/AIDS to "Stop cost being an obstacle".

Bernhard Schwartlander, Director of the Evidence, Strategy and Results Department at UNAIDS, told IRIN/PlusNews that short-term investments in developing and rolling out better ARVs could radically reduce non-drug related costs in the mid- and long-term.

A smart investment

Starting patients on treatment earlier is integral to the successful implementation of Treatment 2.0, and is in line with the latest guidelines from the World Health Organization.

Earlier treatment would require an initial increase in funding, but UNAIDS argues that the reduced need for hospitalization and treatment of opportunistic illnesses, as well as the potential to avert countless new infections, would eventually save money.

"We are living in a very resource-constrained situation," said Schwartlander, admitting that it would be difficult to convince donors and governments to increase AIDS funding in the current economic climate. "But what we see is that thinking is more and more shifting to seeing treatment as a very smart investment."

Treatment 2.0 also incorporates various strategies for simplifying and improving HIV treatment that already have a proven track record, including the use of local, community-based organizations to deliver HIV services to hard-to-reach but high-risk populations, such as injecting drug users and sex workers.

Organizations like The AIDS Support Organization (TASO) in Uganda, and the Treatment Action Campaign (TAC) in South Africa, are cited as examples of the successful use of community-based approaches to mobilize people infected and affected by HIV to become advocates, educators and service providers.

UNAIDS consulted extensively in drafting Treatment 2.0 and Schwartlander is optimistic that its positive, can-do approach will motivate the various sectors of the AIDS community that have tended to operate "in silos and sporadically" to work together to overcome the many obstacles to its implementation.

"So far the response has been very positive," he said. "It may be a way to re-inspire the major donors and the countries themselves."

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Africa: Antibiotic Plus ARVs could Halve HIV Mortality - Study. 29/3/10

The group that took co-trimoxazole alongside ARVs, mortality was half what it was in the group which started on ARVs alone.

29 March 2010

NAIROBI - A cheap, widely available antibiotic given to patients when they start taking life-prolonging antiretroviral (ARV) drugs could reduce HIV mortality in resource-limited settings by up to 50 percent says a new study published in the scientific journal, The Lancet.

"We studied patients who were starting HIV treatment and found that in the group that took co-trimoxazole alongside ARVs, mortality was half what it was in the group which started on ARVs alone," Prof Diana Gibb, of the United Kingdom's Medical Research Council (MRC), a co-author of the study, told IRIN/PlusNews.

"We know that ARVs on their own reduce HIV mortality by as much as 90 percent; what our study found was that the use of co-trimoxazole reduces it further still."

The observational study analyzed 3,179 Ugandan and Zimbabwean participants from the Development of Anti-Retroviral Therapy in Africa (DART) trial, conducted by the MRC in Uganda and Zimbabwe, for almost five years. All participants had a CD4 count - a measure of immune strength - of below 200 at the start of the study.

The United Nations World Health Organization recommends co-trimoxazole prophylaxis for all HIV-infected patients with a CD4 count below 350, particularly in resource-limited settings where bacterial infections and malaria are commonplace in HIV-positive people.

Despite these guidelines, the DART study found that the use of the antibiotic was inconsistent in Uganda and Zimbabwe, usually "initiated or continued at discretion of the treating clinician".

"Co-trimoxazole is very low-cost, it's generic and manufactured locally in many African countries, so it is widely available and is already in wide use as a treatment for infections such as pneumonia," Gibb said. "It's a pill a day - just a few [United States] cents."

A 2008 study among HIV-infected children in Zambia found co-trimoxazole prophylaxis "highly cost-effective".
Other than a small number of patients developing a rash, Gibb said, there were hardly any side effects. An added benefit of using the antibiotic was a reduced frequency of malaria, which is endemic in Uganda.

The study recommended co-trimoxazole prophylaxis for at least 72 weeks in all adults starting combination ARVs in Africa.

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Africa: Giving a Voice to Unpaid HIV Care Workers. 7/6/10

'The voices of carers speak to their daily struggles with life decisions that have socio-economic and political implications for their families and communities'

By 7 June 2010

'The voices of carers speak to their daily struggles with life decisions that have socio-economic and political implications for their families and communities' - Dr Meena Shivdas

The crucial role of unpaid carers looking after people living with HIV/AIDS should be urgently recognised as a missing part of the treatment equation.

In a statement prepared for the 9th Commonwealth Women's Affairs Ministers Meeting (9WAMM), a group of 16 Commonwealth parliamentarians said the invisible and unvalued contribution of unpaid care workers impacted negatively on the wellbeing of families.

The parliamentarians and researchers met in Barbados over the weekend for an advocacy workshop to discuss research on the gender and policy dimensions of unpaid HIV care.

"At the centre of the AIDS response are the 12 million people who urgently require access to treatment, care and support. Eight million people who require treatment but do not have access to it are care for at home mostly by women and children, especially girls. These unpaid carers are the missing factor in the treatment equation," they said.

This was particularly pertinent in the context of the global public debt crisis, which will have a huge impact on HIV treatment and care, with cutbacks impacting on healthcare. "It is imperative that we place the unpaid HIV carer in the household as part of the core response to HIV," they agreed.

The workshop was organised by the Commonwealth Secretariat and the Commonwealth Parliamentary Association (CPA).

Worldwide, there are 33.4 million people living with HIV and nearly two thirds of them are Commonwealth citizens. Over half are women.

Dr Meena Shivdas, Advisor at the Secretariat's Gender Section said that the research was undertaken as a response to a paper on financing gender equality in HIV interventions, presented when Women's Affairs Ministers last met in Uganda in 2007.

"This paper set off discussions on unpaid full time HIV care and the need to amplify the voices of carers to make the links between the dignity and rights of carers and the economics of policy and programme decisions on HIV.

"The voices of these carers -- women, men and children -- speak to their daily struggles with life decisions that have socio-economic and political implications for their families and communities."

Countries covered in the research were Bangladesh, Botswana, Canada, Guyana, India, Jamaica, Namibia, New Zealand, Nigeria, Papua New Guinea and Uganda.

The research was undertaken by Professor Marilyn Waring, a former MP from New Zealand and CPA member whose extensive work on women's unpaid work is globally acknowledged. She is currently at the Auckland University of Technology. Dr Robert Carr, the author of the paper that set off the research, is the Director of ICASO, and a global HIV activist. Associate Prof Anit Mukherjee is a health economist at the National Institute of Public Finance and Policy, New Delhi, and a lead author of the AIDS Commission in Asia report. Dr Shivdas is the fourth member of the team, and works on human rights, the law and HIV.

 

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Africa: Hunting for a 'Cure' for HIV. 23/7/10

A successful microbicide trial and the promise of HIV treatment as prevention have dominated the scientific breakthroughs

23 July 2010

Vienna — A successful microbicide trial and the promise of HIV treatment as prevention have dominated the scientific breakthroughs making headlines at the International AIDS Conference in Vienna, but scientists working on a cure for HIV say they are making slow but significant headway in finding a permanent solution to the epidemic.

The main focus of current research is how to find and tackle "reservoirs" - cells, organs or tissue in the body where the virus could remain latent - and eventually become active again.

"Cells harbour HIV for long periods of time, and there are so many different types of cells that move all over the body; these reservoirs can be located anywhere these cells can reach," said Maureen Goodenow, a professor of pathology at the University of Florida.

Current research is seeking a "functional cure", which would not eliminate the virus from the body but would allow a patient's immune system to control the virus without the need for lifelong medicine by using antiretroviral (ARV) drugs and medications for a limited period to target these reservoirs. At least two clinical trials are underway in France to test such products.

"[HIV] treatment can reduce the viral load in the blood but it cannot eliminate it; it's life-long and can have many side effects after long-term use," said Prof Francoise Barré-Sinoussi, who earned a Nobel Laureate in Medicine for her role in the discovery of HIV.

"We are trying to find a treatment that is more efficient, causes fewer complications, and can be stopped after a while; one that would improve a patient's quality of life," she told IRIN/PlusNews.

Stem cell research

In terms of funding, the search for a cure is the poor relation to HIV prevention research. Scepticism about the possibility of finding a cure for such a complex virus, and a lack of significant strides in the field over the last 30 years, have made donors reluctant to support this arm of research.

In 2009 the National Institute of Allergy and Infectious Diseases (NIAID) at the United States National Institutes of Health (NIH), one of the largest donors to global HIV research, spent just over US$40 million - about three percent of its total AIDS spending - on the search for a cure.

"For many years there was a staleness in the field, but now there are a number of breakthroughs, including stem-cell technology, that make it feasible to address the issue," said Carl Dieffenbach, director of the AIDS division at NIAID. "The NIH now plans to ramp up its efforts to find a cure."

The excitement over stem-cell research was caused by a case known as "the Berlin patient". In 2007 Dr Gero Hütter, the doctor treating the Berlin patient - an HIV-positive American leukaemia patient who lived in Berlin - replaced the patient's bone marrow cells with those from a donor with a naturally occurring genetic mutation that rendered his cells immune to HIV.

To date the Berlin patient, who is no longer on ARVs, shows no evidence of having the HI virus.

Researchers in the US are using the same genetic mutation to do stem-cell research in mice in the hope that, eventually, it could provide immunity to HIV-infected patients. Recent positive results have increased interest in this line of research.

Back to basics

But scientists believe that they also need to do more fundamental research into exactly how the virus works. "There is a dearth of information on the basic immunological system, on the molecular interaction between the virus and cells," Goodenow said.

Dieffenbach noted that Hütter, the Berlin patient's doctor, was a haematologist and not an HIV specialist, and said there was a need to collaborate more closely with scientists from diverse fields, from immunologists and virologists to basic scientists and drug developers.

Jean-Francois Delfraissy, director of France's National Agency for AIDS Research, commented: "The real cure - the total eradication of HIV from the body - is a very big task, but we are hopeful that we are taking baby steps towards controlling the virus in infected patients."

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Africa: More than Five Million People Receiving HIV Treatment. 20/7/10

AN estimated 5.2 million people were receiving life-saving HIV treatment at the end of 2009

20 July 2010

Vienna — AN estimated 5.2 million people were receiving life-saving HIV treatment at the end of 2009, according to the latest update from the World Health Organization (WHO).

WHO estimates that 1.2 million people started treatment in 2009, bringing the total number of people receiving treatment to 5.2 million, compared to 4 million at the end of 2008.

"This is the largest increase in people accessing treatment in a single year. It is an extremely encouraging development," says Dr Hiroki Nakatani, WHO Assistant Director-General for HIV, Tuberculosis, Malaria and Neglected Tropical Diseases.

At the ongoing XVIII International AIDS Conference, WHO is calling for earlier treatment for people with HIV. The objective is to begin HIV treatment before they become ill because of weakened immunity.

"Starting treatment earlier gives us an opportunity to enable people living with HIV to stay healthier and live longer," says Dr Gottfried Hirnschall, WHO Director of HIV/AIDS.

Estimates developed through epidemiological modelling suggest that HIV-related mortality can be reduced by 20 percent between 2010 and 2015 if these guidelines for early treatment are broadly implemented.

Earlier treatment can prevent opportunistic infections including tuberculosis (TB), the number one killer of people with HIV. Deaths from TB can be reduced by as much as 90 percent, if people with both HIV and TB start treatment earlier.

The strength of a person's immune system is measured by CD4 cells. A healthy person has a CD4 count of 1000 - 1500 cells/mm3.

WHO previously recommended starting HIV treatment when a person's CD4 count drops below 200 cells/mm3 but now advises starting HIV treatment at 350 cells/mm3 or below.

"In addition to saving lives, earlier treatment also has prevention benefits. Because treatment reduces the level of virus in the body, it means HIV-positive people are less likely to pass the virus on to their partners," Dr Hirnschall says.

WHO's treatment guidelines expand the number of people recommended for HIV treatment from an estimated 10 million to an estimated 15 million. The cost needed for HIV treatment in 2010 will be about USD 9 billion, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS).

"The investments we make today cannot only save millions of lives but millions of dollars tomorrow," said Dr Bernhard Schwartlander, Director, Evidence, Strategy and Results, UNAIDS. "People with weaker immune systems who come late for treatment require more complex and costly drugs and services than those who start treatment earlier and are healthier."

Since 2003 which marked the launch of the historic "3 by 5" initiative to provide access to HIV treatment to 3 million people living in low- and middle-income countries by the end of 2005 the number of people receiving HIV treatment has increased 12-fold.

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Africa: Survey Reveals Gaps in Doctor-Patient Dialogue. 26/7/10

Conversations healthcare providers aren't having with their HIV-positive patients with potentially negative consequences for their treatment and health.

26 July 2010

Johannesburg — A new, global survey has revealed the conversations healthcare providers aren't having with their HIV-positive patients with potentially negative consequences for their treatment and health.

The AIDS Treatment for Life International Survey (ATLIS 2010) of more than 2,000 HIV-positive patients in 12 countries around the world, found that most respondents also had health conditions such as depression, hepatitis C or kidney disease, which could affect their antiretroviral (ARV) treatment, but less than half had ever discussed these with their healthcare providers.

Similarly, about half the respondents said their ARV medication had had a negative impact on their lives, but only 43 percent had ever asked their doctor about new treatment options with fewer side effects.

Patients in South Africa, which has the world's largest ARV programme, reported high levels of adherence - 83 percent said they had not missed a dose in the past month - second only to Brazil, where adherence was almost 90 percent. People living with HIV in Africa and Latin America were also generally more likely to report knowing practical tips for maintaining adherence than those in North America, Europe and Asia.

However, only 62 percent of respondents in Africa knew that the development of drug resistance was a negative consequence of missing ARV doses, and 18 percent of respondents globally thought it was a "good" thing.

Researchers presenting the report's findings at the International AIDS Conference in Vienna, Austria, last week described the lack of patient knowledge about the danger of drug resistance as a major concern.

A statement by the International Association of Physicians in AIDS Care (IAPAC), which commissioned the study, said the research indicated a need for more wide-ranging and in-depth discussions between patients and doctors.

IAPAC president Dr Jose Zuniga commented: "Expanding patient-physician conversations to include all aspects of a patient's wellbeing is crucial for long-term survival and positive treatment outcomes."

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Africa: Worrying Rates of Second-Line Treatment Failure. 4/8/10

Patients with HIV on second-line antiretroviral (ARV) treatment are significantly more likely to experience treatment failure

4 August 2010

Johannesburg — Patients with HIV on second-line antiretroviral (ARV) treatment are significantly more likely to experience treatment failure than those on first-line treatment, according to new research by health NGO Médecins Sans Frontières (MSF).

Published in the Journal of the American Medical Association (JAMA), the MSF study looked at the treatment outcomes of 632 patients in resource-limited settings in Africa and Asia. The research found that patients who started second-line treatment at CD4 counts below 200, and who adhered to treatment less than 80 percent of the time, were more likely to experience treatment failure on second-line ARV regimens.

The research also showed that patients who had two of their nucleoside reverse transcriptase inhibitors (NRTIs) [a class of ARV medication] drugs changed at the start of second-line therapy were less likely to experience treatment failure than those who only had one of this kind of ARV changed.

NRTIs interfere with the ability of the HI virus to replicate itself and are usually given in combination with other ARVs. Patients given combination, or "boosted" protease inhibitors - an ARV that blocks an enzyme crucial to replication - also experienced better treatment outcomes.

In total, nearly 20 percent of the patients who received second-line therapy for more than six months experienced treatment failure, and five percent died.

As ARV access improves in developing countries, an increasing number of patients will eventually need second-line drugs, which are used when patients stop responding to first-line regimens. According to the authors, preventing treatment failure in such patients is paramount because third-line drugs are either unaffordable or unavailable in many of these countries.

The importance of specific ARVs in the treatment outcomes of second-line patients reaffirmed the need for a better and more varied ARV arsenal in developing countries, said lead author and MSF researcher Dr Mar Pujades-Rodriguez.

Although the World Health Organization (WHO) recommends incorporating boosted protease inhibitors into second-line regimens, almost half of the patients surveyed in the study were not on this type of drug, said Pujades-Rodriguez.

Second-line patients were 46 percent more likely to fail treatment than first-line patients, which the researchers attributed to the higher number of side effects associated with second-line drugs, and the greater likelihood of such patients experiencing drug resistance and treatment fatigue as a result of being on treatment longer.

The study also revealed that patients in rural areas, and those treated at primary health care facilities, were less likely to fail treatment than those treated at urban centres and hospitals.

"Health facilities in rural areas might be able to offer a more personalized approach and better psychological support to patients, enabling them to achieve and sustain better levels of adherence to therapy," Pujades-Rodriguez told IRIN/PlusNews.

"Urban sites are likely to treat many more patients, [who] frequently arrive with more severe diseases, and there might be less time available for the follow-up of stable patients."

Given the likelihood of treatment fatigue and negative experiences with first-line drugs, psycho-social support was particularly important to patients on second-line treatment, she said.

"These patients are likely to have experienced periods of sub-optimal adherence because of environmental, personal, or clinical reasons," she pointed out. "Understanding the difficulties faced by these patients is essential to help them to develop strategies allowing them to take their treatment correctly."

Recommendations in the study included improving the availability of second-line ARVs with fewer side-effects and in fixed-dose combinations [multiple ARVs combined in one pill] in developing countries.

The authors also called for better availability of diagnostic equipment to allow healthcare workers in resource-limited settings to diagnose treatment failure earlier, and at higher CD4 counts.

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Atorvastatin and Rosuvastatin have Most Favourable Impact on Lipids of Patients with HIV. 11/1/10

Greater declines in total cholesterol, LDL-C, triglycerides, and non-HDL C values

AIDSMap

By Michael Carter

Atorvastatin and rosuvastatin have the biggest impact on lipid levels in HIV-positive patients, a US study published in the February 1st edition of Clinical Infectious Diseases shows.

Investigators compared the impact of atorvastatin, pravastatin and rosuvastatin on the lipid profiles of 700 HIV-positive adults. More favourable results were seen in patients treated with atorvastatin and rosuvastatin. The safety of the three drugs was comparable, and the rates of serious side-effects and treatment discontinuation because of toxicity were low.

“HIV-infected patients in clinical care who received rosuvastatin or atorvastatin had greater declines in total cholesterol, LDL-C, triglycerides, and non-HDL C values than those patients who received pravastatin,” comment the investigators, who also note “the greatest improvements in dyslipidemia was observed among those who received rosuvastatin.”

Increased blood lipids are common in HIV-positive patients and can increase the long-term risk of serious illnesses such as cardiovascular disease. Guidelines recommend the use of statins to treat high lipids in patients with HIV. However, there is currently little information about the comparable safety and effectiveness of individual statins when used in this population.

Investigators from the University of Alabama and the University of Washington, Seattle, therefore performed a retrospective study including HIV-positive adults who were treated with statins between 2000 and 2008. The impact of the most commonly used statins on lipid profiles was compared. The safety of the drugs was also analysed.

Most of the patients (86%) were men, and the mean age when statin therapy was started was 43 years.

The three most commonly prescribed statins were atorvastatin (43%), pravastatin (40%) and rosuvastatin (14%).

Median starting doses were 10 mg for atorvastatin, 20 mg for pravastatin and between 5 and 10 mg for rosuvastatin. By the end of the study, median doses were 20 mg for atorvastatin, 40 mg for pravastatin and 10 mg for rosuvastatin.

Treatment with the statins improved the patients’ lipid profiles.

After twelve months, mean total cholesterol had fallen by 15%, LDL-cholesterol by 13%, triglycerides by 20% and non-HDL-cholesterol by 17%.

However, outcomes were better for those taking atorvastatin and rosuvastatin than for patients treated with pravastatin. Total cholesterol was significantly lower in patients taking these drugs, as was LDL-cholesterol, and non-HDL cholesterol.

Compared to those taking pravastatin, individuals treated with rosuvastatin also had significantly greater falls in triglycerides (p = 0.03).

After twelve months of therapy 71% of patients had met national US guidelines for cholesterol control.

But once again, outcomes differed according to the statin patients were taking.

Those treated with rosuvastatin (p = 0.03) and atorvastatin (p = 0.001) were significantly more likely than those taking pravastatin to reach the target for LDL-cholesterol reduction.

In addition, those treated with rosuvastatin were more likely than individuals taking pravastatin (p = 0.045) to reach the non-HDL-cholesterol reduction target.

Treatment was generally safe and well tolerated. Overall 6% of patients stopped statin therapy because of side-effects, and the rates of discontinuation did not differ significantly between the three drugs.

Side-effects were reported by 44 patients, and 15 (2%) had potentially serious changes in their liver or kidney function.

Traditionally, pravastatin has been the preferred statin for use in HIV-positive patients. This is because of its low risk of interactions with antiretrovirals. “However,” write the investigators, “our findings suggest that the lipid-lowering effectiveness of pravastatin was significantly less than that of rosuvastatin or atorvastatin.”

The investigators conclude, “our findings are consistent with the recent British guidelines that include a recommendation to use rosuvastatin.”

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Cheap Antibiotic Halves Risk of Death in First 18 Months of Antiretroviral Treatment. 1/4/10

Use of cotrimoxazolee, cut the death rate by half in the first 72 weeks on antiretroviral therapy in over 3000 HIV-infected patients

AIDSMap

1 April 2010
By Carole-Leach Lemens

Use of cotrimoxazole, a cheap and widely available antibiotic, cut the death rate by half in the first 72 weeks on antiretroviral therapy in over 3000 HIV-infected, symptomatic and severely immunosuppressed patients in Uganda and Zimbabwe, Sarah Walker and colleagues reported in an analysis of the DART trial published on March 29 in the online edition of The Lancet.

During the first 72 weeks after starting antiretroviral therapy cotrimoxazole reduced the risk of death by 56% (95% confidence interval 0.37 to 0.86, p=0.02). Its use also contributed to a 26% reduction in the risk of a first episode of malaria.

Cotrimoxazole is used in resource-poor settings to treat and prevent community-acquired infections, and it is known to be effective against a number of HIV-related infections including pneumocystis jirovecii pneumonia and toxoplasma gondii.

Based on research findings from the United States, the World Health Organization (WHO) recommends cotrimoxazole prophylaxis use in all symptomatic adults with CD4 counts under 350 cells/m3 in resource-poor settings.

However there are wide variations between countries in its availability and use. Concern about its benefits and toxicity when used with ART, as well as concerns about adherence, are the primary reasons. Yet few data, if any, exist to validate these concerns.

Studies have shown that people starting ART in sub-Saharan Africa have a high mortality rate ranging from 8 to 25%, with most deaths occurring within the first three to six months. The high rate of early mortality is a consequence of the severe immunosuppression present in people starting treatment. In the early months of treatment people may die from pre-existing opportunistic infections, or acquire new illnesses.

Late diagnosis of HIV infection and very late initiation of treatment mean that many people with HIV do not receive cotrimoxazole prophylaxis prior to starting antiretroviral therapy.

Nevertheless, cotromixazole may have a protective effect against new infections after starting treatment.

The prinicipal investigators of the DART study undertook an observational analysis of participants from the DART randomised trial of management strategies, in order to evaluate the impact of cotrimoxazole prophylaxis in people starting ART in the study.

The participants, all with CD4 counts under 200 cells/mm3, didn’t use cotrimoxazole routinely, nor was it randomly assigned. Each treating physician decided when to start and stop its use.

The authors wanted to estimate the effect of cotrimoxazole use, after starting ART, on survival, WHO stage 3 or 4 events, malaria, CD4 cell count, body-mass index (BMI), and blood indices.

The 3179 participants from four centres (two clinical centres in Uganda: the Medical Research Council/Uganda Research Unit on AIDS, Entebbe; and the Joint Clinical Research Centre, Kampala, with a satellite clinic at the Infectious Diseases Institute, Mulago, and one centre in Zimbabwe: University of Zimbabwe, Harare) included in the analysis contributed a total of 14,214 years of follow-up, with 57% or 8128 person-years on cotrimoxazole.

Use of cotrimoxazole varied between the four centres (15%, 72%, 72% and 79%).

ART adherence was high in those who were currently taking cotrimoxazole or had used it.

Present cotrimoxazole use cut death rates by 50% within the first twelve weeks regardless of centre, whether prophylaxis started before ART or at the same time as ART. The authors stress that survival benefits are restricted to present use.

Not surprisingly factors that were linked to increased mortality included low CD4 cell count, haemoglobin concentration or body mass index, or those with a WHO stage 3 or 4 event in the preceding 4 weeks or any stage 3 or 4 event since the randomisation. These same factors were also associated with the increased probability of cotrimoxazole use.

The benefits of cotrimoxazole, however, did decline with time on ART, decreasing from a 58% reduction in the risk of death within the first four weeks on ART to 5% in weeks 68 to 72. After this point no further reductions were seen.

The authors discuss several potential explanations for why the benefit appears greater in the first 72 weeks of antiretroviral treatment than after that point.

One possibility might be that cotrimoxazole no longer provides any additional benefit once a certain CD4 level has been reached, indicating a more competent immune system.

In fact, the investigators found no relationship between CD4 count and the magnitude of cotrimoxazole’s effect: people with low CD4 counts after 72 weeks were no more likely to die from infections that might be prevented by cotrimoxazole after this point than people with high CD4 counts.

Another possibility is that although cotrimoxazole doesn’t increase the CD4 count, it may reduce the severity of infections and so reduce the risk of death. But this doesn’t explain why it stops having this effect after 72 weeks.

The authors suggest one hypothesis, that cotrimoxazole lowers the amount of bacteria in the gut and limits movement of bacteria into the bloodstream, so reducing immune activation and improving immune response. However, the mechanism by which a decrease in immune activation might lead to a reduced susceptibility to life-threatening illness is not explained, and this relationship cannot be explored further in this population due to the lack of appropriate stored samples.

Cotriomoxazole use had no effect on new WHO stage 4 events, CD4 cell counts or body mass index. It also had no effect on the incidence of tuberculosis.

However the incidence of malaria was reduced by 26%. In Uganda, where malaria is endemic, the effect on the reduction of malaria was sustained with use beyond 72 weeks. The authors note these findings are consistent with other reports of the benefits of cotrimoxazole against malaria in semi-immune adults.

Semi-immune in this context is described as individuals born and living in an endemic area compared to those described as non-immune, those who have not grown up in such an area. Malaria is not fatal in semi-immune adults, nor is cotrimoxazole the preferred treatment option.

The authors acknowledge the value of randomised trials to secure the best evidence for patient management. Yet, they add, effective management has to happen with or without them. Their study, they note, was observational, so bias cannot be ruled out.

However, the data came from a randomised trial where key clinical and laboratory findings used by clinicians for patient management were acquired systematically and prospectively. The large cohort size together with consistent results across the four centres added strength to their findings, note the authors.

The authors propose that since the characteristics of DART participants are similar to most patients starting ART in sub-Saharan Africa their findings should be generalisable.

The authors conclude “the mortality benefits, safety, and tolerability, together with the low cost and simplicity of implementation suggest that cotrimoxazole prophylaxis is cost-effective and has a substantial public health effect. Our results reinforce WHO guidelines and provide strong motivation for at least 72 weeks to all adults starting ART in Africa.”

Reference
AS Walker et al. Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort. The Lancet, online edition, DOI:10.1016/S0140-6736(10)60057-8, March 29, 2010.

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Child Development Affected by Late Treatment Start in Resource-Limited Settings. 20/7/10

Earlier initiation of treatment for optimum growth is strongly indicated in the light of these findings

AIDSMap

By Carole-Leach Lemens
20 July 2010

Children infected with HIV in resource-poor settings are at a significant risk for developmental impairment – affecting neurocognitive functions as well as growth – in spite of increased access to antiretroviral treatment, researchers reported at the Eighteenth International Conference on AIDS in Vienna on July 19.

Earlier initiation of treatment for optimum growth is strongly indicated in the light of these findings, said researchers from the Perinatal HIV Research Unit, Soweto, and colleagues in Vancouver. They found that children who had started treatment with a CD4 count over 200 had better improvements in weight-for-age and height-for-age scores after starting treatment.

Another study in Jamaica showed that healthcare workers having appropriate screening tools to detect the signs and symptoms of neurological damage (and referring to appropriate treatment and services) as children move into adolescence will be key to mitigating the impact of HIV in children.

In additional, Luminita Ene and colleagues in Romania reported that the presence of viral subtype F may worsen neurological problems.

They found a high prevalence of neurocognitive impairment and of AIDS-defining opportunistic infections among a cohort of HIV-infected Romanian children,  a homogenous group that included those exposed to HIV clade F and who had been on combination antiretroviral treatment for at least ten years.

Among 528 children treated between 1996 and 2008, 43.7% (231) had central nervous system complications. While the number of cases of HIV encephalopathy and opportunistic central nervous system infections decreased with the introduction of combination antiretroviral treatment, the proportion within all AIDS-defining illnesses remained unchanged.

In Jamaica, researchers conducted a two-part analysis (consisting of a database review and a prospective nested case-control study ) of the neurological outcomes of infected children at four paediatric clinics in the Greater Kingston Metropolitan Area of Jamaica from September 2002 to August 2008. Samantha Walker and colleagues found that 23.3% (67) of the children had been diagnosed with HIV encephalopathy, at a median age of 1.57 years (IQR: 1.08 to 3.43).

The primary neuro-developmental abnormalities at diagnosis included: delayed growth (88%); hyperreflexia (being overactive, causing twitching, muscle tension) (88%); spasticity (muscle tension and stiffness) (65%); microcephaly (small skull circumference for age) (63%); and quadriparesis (muscle weakness in all four limbs) (31%).

No significant changes in neurodevelopmental abnormalities were seen after one year on antiretroviral therapy.

Children who had previously been diagnosed  with HIV encephalopathy had difficulty with concept-forming tests, poor short-term memory and inconsistent attention spans, and small skull circumference (for age), as well as needing more time to complete tests that required motor-skill co-ordination, compared to the case controls.

Dr Walker said it was possible that antiretroviral treatment may have started after irreversible central nervous system damage had already happened. She stressed the importance of having feasible, cost-effective screening tools for early detection of neurocognitive impairment to allow for appropriate intervention strategies – for example, rehabilitation services – particularly as children grow into adolescence.

Erica Maxine Lazarus and colleagues reported on a retrospective cross-sectional analysis at the Perinatal HIV Research Unit in Soweto, South Africa, of adolescents (aged 11 to 19 years) on antiretroviral therapy, to look at the effects of baseline CD4 cell count (categorised as above and below 200 cells/mm3), viral response (categorised as above and below 400 copies/ml), and length of time on treatment, on growth.

Of the 107 adolescents, median age at the start of antiretroviral treatment was 8.4 years (IQR: 6.07 to 11.4), and 14.75 years (IQR: 13.49 to 16.47) at the time of the review. Median time on antiretroviral therapy was 6.1 years (IQR: 2.4 to 9.1).

Fifty-nine per cent of the adolescents had a CD4 cell count greater than 200 cells/mm3 at the start of treatment. Eighty-four per cent had viral loads under 400 copies/ml at their most recent visit. Of the four measures (CD4 cell count; baseline age; length of time on treatment; and most recent viral load), baseline CD4 cell count alone was associated with significant increases in height.

Children with CD4 cell counts greater than 200 cells/mm3 at the start of treatment had almost three times the odds of improved height compared to those with baseline CD4 cell count under 200 cells/mm3.

For best growth outcomes into adolescence, Dr Lazarus and her colleagues recommended starting antiretroviral treatment in children over five years of age with CD4 cell counts over 200 cells/mm3

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Community Statement on the START Trial and the Change in the US DHHS Treatment Guidelines. 4/5/10

The following statement is produced in response to a change in the US treatment guidelines in December 2009 that stated that antiretroviral (ARV) treatment should be universally started at any CD4 count below 500 cells/mm3.

4 May 2010

The following statement has been sent to the chairs of the United States Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents.

For media comment, please contact:

  • Dave Munroe, INSIGHT Community Advisory Board, David Munroe, DavidM4239@AOL.COM
  • Nathan Geffen, Treatment Action Campaign, on +27 (0) 84 542 6322
  • Simon Collins, HIV i-Base, on +44 (0) 20 7407 8488

Introduction

The following statement is produced in response to a change in the US treatment guidelines in December 2009 that stated that antiretroviral (ARV) treatment should be universally started at any CD4 count below 500 cells/mm3.

The START study is currently enrolling patients to look at whether there is evidence to support such a recommendation. Currently no randomised trial has provided data on the advantages and risks of earlier treatment. This statement affirms both the importance of the START trial and the safety for people who enrol.

We believe that the priority for HIV-positive people is to have accurate, reliable data on both the risks and benefits of earlier treatment in order to base any decision for when to start treatment.

Statement

When to start antiretroviral treatment is one of the most important outstanding questions for people with HIV and their clinicians. A large clinical trial, Strategic Timing of Antiretroviral Treatment (START), has begun and will hopefully help answer this and other important questions.

The START trial includes antiretroviral-naive HIV-positive people with CD4 counts greater than 500 cells/mm3. It is taking place at about 90 sites in nearly 30 countries. Participants are randomised to either receive antiretroviral treatment immediately or to defer treatment until their first CD4 count less than 350 cells/mm3 or they have clinical signs of AIDS. Eventually, START will recruit 4,000 people.

The deferred arm is the current standard of care throughout the world, with guidelines recommending treatment at a CD4 count of 350 cells/mm3. Clinical trials have demonstrated that once the CD4 count drops to below 350 cells/mm3, antiretroviral treatment should begin. However, the recent US guideline change requires a community response for US patients who still want to take part in this study.

On 1 December 2009, the United States (US) Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents were changed to recommend treatment for patients with CD4 counts between 350 and 500 cells/mm3. Of the more than two-thirds of Panel members who supported this recommendation, 55% recommended it strongly and 45% moderately.  As explained in the guidelines, this recommendation is based solely on observational data primarily from two large cohorts known as ART CC and NA-ACCORD. As with all observational data the findings from these cohorts could be subject to confounding factors.

Indeed, the ART CC investigators have stated, “We are concerned that some may interpret the new [US] recommendations as implying that the deferral group of this trial is no longer ethical. Such an interpretation would endanger the future of the trial in the [US].”

They further state, “We … do not believe that there is convincing evidence to conclude that deferral of initiation of ART to a CD4 count of [350 cells/mm3] causes net harm, particularly in terms of mortality, compared with starting at any higher level. We strongly support continued enrolment into START. Large randomised studies represent the only means of eventually obtaining the definitive result we need to properly inform future patient care.

We agree with the ART CC investigators. The available evidence is insufficient to determine if the adherence challenges and long-term side-effects of early antiretroviral treatment are outweighed by reduced risk of illness conferred by these medicines. Only a randomised controlled trial, such as START, can determine this.

The NA-ACCORD data is also challenged by the researchers who orginally developed the new statistical methodology. They were not convinced that the application thereof was without problems.

We too are concerned that the new US recommendation:

(1) raises theoretical concerns about continued enrolment of patients in the US, a substantial source of patients, and
(2) is based on poor evidence and therefore might not be in the best interests of patients.
We also have further concerns that:
(3) previous recommendations to use earlier treatment failed to recognise the negative impact of resistance and side effects, and
(4) a minority of individuals have normal CD4 counts between 350-500 and would therefore be using treatment prior to any significant immune damage.

We support research findings that the absolute risk of HIV-related complications remains very low at a CD4 count 350–500 and that individuals enrolled in START will be carefully monitored and access treatment if their health circumstances change.

We also support the unique importance of sub-studies in START.

These studies have the potential to answer important questions relating to the impact of HIV, treatment and ageing on neurology and mental health, bone health, heart disease, lung disease and behaviour risk.

We support the START investigators, community advocates and HIV-positive people interested in this dynamic research which will help close the essential gap in our current knowledge on the safety and risks of earlier treatment.

Signed:
(Members of the INSIGHT Community Advisory Board in surname alphabetical order)
Peer Aagaard, Denmark
Simon Collins, London
Nathan Geffen, South Africa
Joseph Hall, USA
David H. Haerry, Switzerland
Michael Meulbroek, Spain
David Munroe, USA
Dwight Peavy, USA
Claire Rappoport, USA
Siegfried Schwarze, Germany
Mirta Valdez, Argentina
Jo Watson, Australia
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Darunavir/Ritonavir as Effective in Women as Men. 22/9/10

Within four weeks of the study starting, women were more likely to withdraw from the trial than men

AIDSMap

By Michael Carter
22 September 2010

Darunavir/ritonavir-based antiretroviral therapy is equally effective in treatment-experienced women and men, US investigators report in the Annals of Internal Medicine.

However, within four weeks of the study starting, women were more likely to withdraw from the trial than men. The investigators believe that this shows that more needs to be done to retain women in clinical trials.

There was no real difference in overall side-effects between women and men, but women were more likely to report nausea.

“Darunavir-ritonavir antiretroviral combinations have similar efficacy outcomes and incidence of adverse-events in treatment-experienced men and women”, comment the investigators.

Women represent a growing proportion of the population affected by HIV. However, they are often under-represented in clinical trials, especially those involving treatment-experienced patients.

If women comprise less than 25% of a study population then the ability of a clinical trial to detect sex-based differences in outcomes is compromised.

Women were under-represented in studies exploring the safety and efficacy of ritonavir-boosted darunavir (Prezista) in treatment-experienced patients. To gain a clearer understanding of the effects of the drug on women, investigators designed the open-label GRACE (Gender, Race, and Clinical Experience) study.

According to the study protocol, 70% of participants were to be women. In addition, the percentage of white men enrolled in the study was carefully monitored, and was limited to less than 25% of the planned study population.

Patients were required to have a viral load of above 1000 copies/ml and experience of treatment with all the three main classes of antiretroviral drugs.

The study medication consisted of 600/100mg darunavir/ritonavir twice daily, plus optimised background therapy. The trial lasted 48 weeks and was conducted between 2006 and 2008.

A total of 429 individuals were recruited to the study. Just over two-thirds (67%) were women and 84% were black or Hispanic.

Women were more likely than men to be black (67% vs. 51%, p = 0.011), but were less likely to have developed an AIDS-defining condition (36% vs. 47%, p = 0.021).

A third of women stopped treatment early compared to 23% of men (difference, p = 0.042). It became apparent as early as week four of the study that more women were withdrawing, and this difference persisted through to week 48.

 Women were more likely than men to be lost to follow-up (8% vs. 6%), or to withdraw because of side-effects (8% vs. 4%). However, neither of these differences was statistically significant.

Treatment adherence of 95% or greater was reported by 64% of women and 69% of men.

In the intent-to-treat analysis, 51% of women compared to 59% of men achieved and maintained a viral load below 50 copies/ml.

When the analysis was restricted to patients who remained on treatment, equal proportions of women and men were found to have had a good virologic outcome to therapy (73% vs. 73%).

Statistical analysis that controlled for baseline viral load and CD4 cell count showed that in the intent-to-treat population, women were approximately 10% less likely than men to suppress their viral load to undetectable levels. However, this was difference was not statistically significant (p = 0.067).

A non-significant difference in treatment response was also seen in the on-treatment analysis.

The investigators believe that these differences had nothing to do with the virologic efficacy of the therapy. Rather they attribute them to the “high number of women who withdrew for reasons other than virologic failure.”

Significantly better (p = 0.033) CD4 cell count increases were observed in women than men.

Rates of confirmed virologic failure were comparable in women and men (29% vs. 28%). The investigators looked at the outcomes of such patients with a viral load above 1000 copies/ml and found that women were slightly less likely than men to develop resistance.

A total of 16% of women and 23% of men experienced serious side-effects. Two women and two men died, but none of these deaths were associated with the study medication.

Comparable proportions of women and men (27% vs. 34%) experienced a grade 3 or 4 side-effect, as well as any side-effect that considered by the investigators to be possibly related to darunavir/ritonavir (47% vs. 43%).

The only side-effects that was significantly more likely to occur in women than men was nausea and vomiting (5% vs. 3%). This did not have any clinical impliations.

 “Virologic response rate did not significantly differ between women and men,” comment the investigators. They add, “overall, darunavir-ritonavir therapy seemed to be well tolerated in our study”.

 They conclude that the study shows that it is possible to recruit large numbers of women to a clinical trial. However, “the high discontinuation rate in women, which was driven by reasons other than failure, highlights the need for additional efforts to retain diverse populations in studies.

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Detectable Genital HIV Shedding Associated with Cervical Infections Appears Minimal among Women taking ART. 1/10/10

“identification and treatment of cervical infections may help to optimize the secondary [HIV] prevention benefits of ART.”

AIDSMap

1 October 2010
By Kelly safreed-Harmon

Results from a small Kenyan study suggest that cervical HIV viral load levels remain low during episodes of cervical infection in HIV-positive women taking antiretroviral therapy (ART).

The finding is of interest to researchers exploring the dynamics of HIV infectiousness in the context of the global scale-up of ART, since viral load reductions resulting from ART usage in some settings may be of a large enough magnitude to bring about population-level reductions in HIV transmission.

Although ART greatly lowers infectiousness overall, detectable levels of HIV persist in the genital secretions of a small proportion of women taking ART.

The fact that cervical infections can increase genital HIV shedding in women not taking ART raises the question of whether the same dynamic might continue operating to some degree in women after they initiate treatment.

The Kenyan study indicates that this is not generally the case. Most study participants who developed cervical infections while taking ART were found to maintain undetectable cervical HIV viral load levels during those episodes. Among the small number of women whose viral load levels surpassed the threshold of detection, viral load levels still remained quite low.

The prospective cohort study enrolled 147 HIV-positive Kenyan women who met standard clinical criteria for ART initiation. The women began taking standard first-line antiretroviral regimens and providing biological samples for monthly viral load and genital infection testing. The viral load threshold of detection was 100 copies/mL.

Researchers analysed data from 30 study participants who experienced 31 episodes of cervical infection at least one month after they had started ART. One case involved the diagnosis and treatment of chlamydia; 17, gonorrhea; and 13, non-specific cervicitis.

From a statistical standpoint, women’s likelihood of developing detectable HIV viral load levels increased with the onset of cervical infections. However, only five women actually had detectable viral load levels and cervical infections concurrently.

The women’s viral load levels ranged from 100 to 820 copies/mL during episodes of cervical infection (median, 115 copies/mL).

The median age of the study subset experiencing cervical infections was 36 (interquartile range, 31 – 38). ART pill counts indicated high treatment adherence levels.

The authors caution that although their results “further highlight the potential benefits of ART as a prevention strategy,” it is important to bear in mind that even low levels of HIV in genital secretions can potentially result in transmission to sexual partners.

Thus, the paper concludes, “identification and treatment of cervical infections may help to optimize the secondary [HIV] prevention benefits of ART.”

The Kenyan study, although too small to yield definitive findings, contributes another piece to the complex picture that is emerging in relation to the concept of HIV treatment also functioning as an HIV prevention tool.

If other researchers concur that cervical infections do not greatly increase HIV-positive women’s likelihood of transmitting the virus to sexual partners, then this can be ruled out as a potential factor in efforts to explain why some people on ART are at greater risk of transmitting the virus onward than are others.

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Earlier Treatment Averting Higher Medical Costs In South African Cohort. 6/1/10

Carole Leach-Lemens,
Wednesday, January 06, 2010

Starting treatment earlier, at a higher CD4 count, and being in care six months or longer before starting ART, is associated with lower treatment costs during the first months of antiretroviral treatment, according to an analysis of the direct health care costs of treating over 10,000 HIV-infected adults in a private HIV care programme in southern Africa, published in the December 1 edition of PLoS Medicine.

Careful monitoring of adherence, including interventions to improve adherence, can reduce costs incurred later, reported Rory Leisang and colleagues. Poor adherence is associated with significant increases in costs over time suggesting, according to the authors, that this should be included in economic models of ART.

Progress toward universal access to treatment in resource-poor settings continues in part because of the reduction in costs of antiretroviral drugs. However, antiretroviral drugs are only one part of the direct cost of treatment.

Other direct costs may include general practitioner, specialist, maternity-related care for patients receiving ART, hospital accommodation, CD4 counts, and/or viral loads (when available).

Effective allocation of limited resources in resource-poor settings requires that public health officials and policymakers have the most complete information possible about the direct costs of HIV care. Few studies have looked at these costs and in particular those incurred before the start of ART.

The authors undertook a retrospective cohort analysis of the direct costs of treating over 10,000 HIV-infected adults enrolled in a Southern African managed care programme with close to 600,000 patient months of follow-up from three years before the start of antiretroviral treatment to five years on ART. In this programme ART was provided when CD4 cell counts fell below 350 cells/mm3.

Direct costs increased from about four months prior to the start of ART and peaked at the start of ART remaining high for the next four months. After this point costs decreased to an intermediary level and remained stable over the next five years.

The authors note an important and unique aspect of their study—the time-dependent association between total costs and specific variables.

Lower baseline CD4 cell counts, higher baseline viral loads and shorter time of CD4 cell count monitoring before the start of ART (a substitute for HIV care) were independently linked with higher costs in the early time period and mostly driven by hospitalisation.

High rates of morbidity ending in hospitalisation or death are common to antiretroviral programmes in resource-poor settings. When compared with resource-rich settings, patients on ART in resource-poor settings have higher early mortality because more often people begin ART at a more advanced disease stage.

Poor adherence was the key variable associated with higher costs in the later time period. Conversely higher adherence was associated with lower costs and in particular when removing antiretroviral drug costs. Poor adherence means limited effectiveness of treatment, greater risk of resistance and failure which may lead to earlier switching to more costly second-line regimens. The authors stress that in spite of the importance of adherence it is not included in current economic models.

The authors note several limitations.

The cohort consists of private sector patients while the majority of patients in resource-poor settings are treated in the public sector. The authors acknowledge that the actual cost findings may not be generalisable to public health care systems in Southern Africa and other resource-poor settings. However, they argue, their findings that the drivers of total costs change considerably over time may be generalisable providing valuable information to public health planners and policymakers.

Also, the impact of specific AIDS-defining illnesses on outcomes and costs were not included because the data were not available.

The analysis is that of a provider’s perspective. While indirect costs and direct non-health costs were not included this perspective, the authors argue, is relevant in determining the key drivers of health care costs.

They note that public health planners need to be concerned with issues other than reducing costs including quality of care and outcomes which although not addressed in the analysis are essential.

Their findings suggest that high early costs of antiretroviral programmes could be reduced by starting ART at higher CD4 cell counts and being in HIV care for longer periods before starting treatment.

In addition monitoring of ART adherence as well as interventions to improve adherence can reduce later direct costs. They conclude: “The increasing impact of ART adherence on costs over time suggests that this variable should be incorporated in economic models of ART.”

Reference

Rory Leisegang et al. Early and late direct costs in a Southern African antiretroviral treatment programme: a retrospective cohort analysis. PLos Med 6 (12): e1000189. doi:10.1371/journal.pmed.1000189. 2009

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Experts Recommend Finetuning of HIV Treatment. 23/2/10

Reuters

HONG KONG (Reuters) - How quickly an HIV patient's immune system deteriorates may not affect the outcome of the illness, a study has found, and this could help change current guidelines for treatment of the disease.

There is no cure for the human immunodeficiency virus (HIV) that causes AIDS, but combinations of drugs can keep the virus from replicating and damaging the immune system.

Doctors normally do not start treatment until there is some evidence of damage to this system, measured by counting the number of immune cells, called CD4 T-cells.

In developed countries, HIV treatment usually begins when CD4 numbers drop below 350 cells per microlitre of blood.

Some treatment guidelines also recommend that therapy be started more quickly for people whose CD4 counts decline rapidly.

But the study, involving an international team of researchers, found that the pace of decline did not result in any substantial differences to the outcome of the illness.

"What we looked at was whether it matters how a person reached his current CD4 cell count, whether the CD4 count declined very quickly, or very slowly, and we found that the CD4 cell dynamics don't provide additional information about the patient's prognosis on top of the current CD4 cell count," said Marcel Wolbers of the Hospital for Tropical Diseases in Ho Chi Minh City in Vietnam.

Wolbers, a biostatistician and one of the principal investigators of the study, and his colleagues examined records of 2,820 HIV patients from Australia, Canada and Europe with varying rates of CD4 declines.

They found no significant differences in their progression to AIDS or the number of deaths.

"The current rate of CD4 cell decline is neither a strong predictor of whether a person is progressing to AIDS or dies, nor does it predict future CD4 cell decline," he said. "Therefore, it shouldn't guide clinical decisions, in particular the decision whether to initiate (drug) therapy or not.

"A further implication of our study is that the patient's CD4 cell count should be monitored regularly regardless of the prior rate of CD4 decline and that should be done according to current guidelines, i.e. every three to six months."

The study, published in the latest issue of PLoS Medicine, is available for free here.

(Reporting by Tan Ee Lyn, Editing by Ron Popeski)

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Global: Hunting for a "Cure" for HIV. 23/7/10

Ssuccessful microbicide trial and the promise of HIV treatment as prevention have dominated the scientific breakthroughs

23 July 2010

Vienna - A successful microbicide trial and the promise of HIV treatment as prevention have dominated the scientific breakthroughs making headlines at the International AIDS Conference in Vienna, but scientists working on a cure for HIV say they are making slow but significant headway in finding a permanent solution to the epidemic.

The main focus of current research is how to find and tackle "reservoirs" – cells, organs or tissue in the body where the virus could remain latent - and eventually become active again.

"Cells harbour HIV for long periods of time, and there are so many different types of cells that move all over the body; these reservoirs can be located anywhere these cells can reach," said Maureen Goodenow, a professor of pathology at the University of Florida.

Current research is seeking a "functional cure", which would not eliminate the virus from the body but would allow a patient's immune system to control the virus without the need for lifelong medicine by using antiretroviral (ARV) drugs and medications for a limited period to target these reservoirs. At least two clinical trials are underway in France to test such products.

"[HIV] treatment can reduce the viral load in the blood but it cannot eliminate it; it's life-long and can have many side effects after long-term use," said Prof Francoise Barré-Sinoussi, who earned a Nobel Laureate in Medicine for her role in the discovery of HIV.

"We are trying to find a treatment that is more efficient, causes fewer complications, and can be stopped after a while; one that would improve a patient's quality of life," she told IRIN/PlusNews.

Stem cell research

In terms of funding, the search for a cure is the poor relation to HIV prevention research. Scepticism about the possibility of finding a cure for such a complex virus, and a lack of significant strides in the field over the last 30 years, have made donors reluctant to support this arm of research.

In 2009 the National Institute of Allergy and Infectious Diseases (NIAID) at the United States National Institutes of Health (NIH), one of the largest donors to global HIV research, spent just over US$40 million - about three percent of its total AIDS spending - on the search for a cure.

"For many years there was a staleness in the field, but now there are a number of breakthroughs, including stem-cell technology, that make it feasible to address the issue," said Carl Dieffenbach, director of the AIDS division at NIAID. "The NIH now plans to ramp up its efforts to find a cure."

The excitement over stem-cell research was caused by a case known as "the Berlin patient". In 2007 Dr Gero Hütter, the doctor treating the Berlin patient – an HIV-positive American leukaemia patient who lived in Berlin - replaced the patient's bone marrow cells with those from a donor with a naturally occurring genetic mutation that rendered his cells immune to HIV.

To date the Berlin patient, who is no longer on ARVs, shows no evidence of having the HI virus.

Researchers in the US are using the same genetic mutation to do stem-cell research in mice in the hope that, eventually, it could provide immunity to HIV-infected patients. Recent positive results have increased interest in this line of research.

Back to basics

But scientists believe that they also need to do more fundamental research into exactly how the virus works. "There is a dearth of information on the basic immunological system, on the molecular interaction between the virus and cells," Goodenow said.

Dieffenbach noted that Hütter, the Berlin patient's doctor, was a haematologist and not an HIV specialist, and said there was a need to collaborate more closely with scientists from diverse fields, from immunologists and virologists to basic scientists and drug developers.

Jean-Francois Delfraissy, director of France's National Agency for AIDS Research, commented: "The real cure – the total eradication of HIV from the body – is a very big task, but we are hopeful that we are taking baby steps towards controlling the virus in infected patients."

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Global: Mortality Data Reveals HIV Treatment Progress. 30/4/10

The study compares adult mortality between 1970 and 2010 in 187 countries.

30 April 2010

Johannesburg - A new study of adult mortality tells the tale of HIV over decades and across borders and how treatment may have helped to rewrite the ending.

Published in The Lancet’s 30 April early online edition, the study compares adult mortality between 1970 and 2010 in 187 countries.

Using data from various sources, including censuses and household surveys, researchers found that HIV was key to reversing the worldwide decline in mortality from 1970 to 1990.

Even though worldwide mortality is still about 26 percent lower than it was 40 years ago, there are regional imbalances. In sub-Saharan Africa, hard hit by HIV, mortality is at levels not seen in developed countries such as Sweden since the 1700s.

But study co-author Christopher Murray of the Institute for Health Metrics and Evaluation at the University of Washington said that while the data bore testament to HIV’s devastating impact, it also revealed a story of hope that was only just beginning to emerge.

“To give you a sense of the impact of HIV, we analysed maternal mortality numbers for all countries in the world and were able to show that 20 percent of all maternal deaths could have been avoided if HIV had not been a factor,” he told IRIN/PlusNews. “An emerging public health success story is the scale-up of antiretroviral [ARV] therapies in Africa, [which] seems to be one of the drivers in the declines in mortality that we have seen in many countries there since 2005.”

According to Murray, the data reinforces arguments for mainstreaming ARV treatment and services aimed at preventing mother-to-child transmission of HIV within maternal health programmes.

However, the study also found that gaps between countries with high mortality rates, such as Zambia and Swaziland, and those with low rates, such as Iceland, continue to widen.

According to UNAIDS, Zambia has an HIV prevalence of about 15 percent while Swaziland has the world’s highest HIV prevalence at 26 percent.

“AIDS continues to be a big problem, despite the improvements there. This is why it is so important for countries to monitor where they are making progress and see what they can do to improve on that progress,” Murray added.

There was a need to improve adult mortality monitoring with better data collection to track not only the impact of HIV but also chronic diseases such as diabetes, alcoholism and heart disease that are emerging as income rises in more countries, he said.

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High Genital HIV Levels may Persist in Women who Appear to Achieve Viral Suppression with Use of ART. 6/9/10

The findings have important HIV prevention implications

AIDSMap

By Kelly Safreed-Harmon
6 September 2010

HIV-positive women whose plasma HIV RNA viral loads drop to undetectable levels following initiation of ART still may have intermittent surges in the amount of virus in their genital secretions, according to a US study.

The study analysed changes over the course of one year in the plasma and genital tract HIV levels of US women taking ART. The journal AIDS has published the findings in an online article released in advance of print publication.

The findings have important HIV prevention implications in light of recent debates about the extent to which HIV-positive people with undetectable plasma viral load are still at risk of transmitting HIV to others.

In particular they highlight the need for evidence of viral load levels in genital secretions to be measured longitudinally in studies which monitor rates of HIV transmission in HIV-discordant sexual partnerships. Gathering these data would permit a better understanding of the clinical significance of episodic shedding of HIV in genital fluids when plasma viral load is suppressed.

Women who had plasma HIV viral load levels below 75 copies/mL at least six months before being screened for the study were eligible to participate. Fifty-nine women who met this requirement, all patients at an HIV clinic in the US state of Rhode Island, contributed a total of 582 study visits at which they underwent plasma and genital tract viral load testing.

More than half of all study participants had detectable genital tract viral load levels (>3300 copies/mL), a condition referred to as “HIV shedding,” at least once during the study period. Almost 40% of women had HIV shedding when HIV was undetectable in plasma.

Among women who had not undergone hysterectomies, the highest genital viral load levels observed in conjunction with undetectable plasma viral load were 456,000 copies/mL in the endocervix; 648,000 copies/mL in the ectocervix; and 480,000 copies/mL in the vagina.

The endocervix, ectocervix and vagina had about the same likelihood of yielding samples with detectable viral load during plasma viral load suppression.

Researchers tested vaginal samples from women who had undergone hysterectomies. In that group, the highest vaginal viral load level when HIV was undetectable in plasma was 68,000 copies/mL.

Researchers considered the potential role of STIs in increasing genital tract HIV shedding, but data on STIs in the study population did not suggest associations of that nature.

Overall, women without hysterectomies had HIV shedding in at least one of the three parts of the vaginal tract at 9% of study visits at which they also had undetectable plasma viral load levels (95% CI, 6% – 14%). Shedding was observed at 13% of all study visits (95% CI, 9% – 18%).

A component of the study looked at genital tract HIV levels over time in women who maintained undetectable plasma HIV viral load levels (less than 80 copies/mL) for at least three consecutive study visits.

Researchers assigned those women one of three classifications.

-“Persistent shedders” were those who had at least two consecutive study visits with undetectable plasma HIV levels but detectable genital tract HIV levels.
-“Intermittent shedders” had undetectable plasma HIV levels but detectable genital tract HIV levels at one visit in between two visits at which both genital tract and plasma HIV levels were undetectable.
-“Nonshedders” never had detectable HIV in the genital tract at the same time that their plasma viral load was below the level of detection.

Four of the 59 study participants (6.8%) were found to be persistent shedders; 18 (31%), intermittent shedders; and 27 (46%), nonshedders. The remaining 10 women did not meet the criterion of having three consecutive study visits with undetectable plasma viral load levels.

Researchers compared the combined group of persistent and intermittent shedders to nonshedders to try to identify sociodemographic and health-related factors that might help account for variations in genital viral load levels.

Women with hysterectomies, who constituted 19% of the study population, were less likely than other women to have genital HIV shedding (risk ratio 0.14, 95% confidence interval [CI], 0.02 – 0.99). No other differences were observed, but researchers noted that some other risk factors could not be ruled out on the basis of the statistical results.

In the full study cohort, having detectable plasma HIV viral load increased the odds of having detectable genital tract HIV viral load at the next visit. The inverse was not true – a detectable genital tract viral load level did not predict a subsequent detectable plasma viral load level.

Antiretroviral treatment failure was not an outcome for any study participant experiencing detectable genital tract HIV levels at the same time that plasma HIV levels were undetectable.

The paper suggests that the “episodic, unpredictable nature of genital tract shedding” in study participants with undetectable plasma HIV viral load levels may make it difficult to assess the HIV transmission risk in such situations.

It concludes, “Whereas genital tract shedding is primarily driven by plasma viremia, clinicians may not be able to solely rely on [ART] to eradicate the potential for the sexual and perinatal transmission of HIV.”

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Huge Variations in Price Paid for Same Antiretroviral Drug between Low-Income Countries. 4/5/10

Prices for some generic antiretroviral drugs varied as much as tenfold between low-income countries, and some middle-income countries paid up to 16 times more than other countries with similar levels of development.

AIDSMap

By Keith Alcorn
4 May 2010

An analysis of prices paid for antiretroviral drugs by 113 countries between 2002 and 2008 shows that prices for some generic antiretroviral drugs varied as much as tenfold between low-income countries, and some middle-income countries paid up to 16 times more than other countries with similar levels of development.

The analysis by Brenda Waning and colleagues at Boston University School of Medicine is published this month in the Journal of Generic Medicines.

Based on data gathered from purchases of antiretroviral drugs with Global Fund grants in 113 low and middle-income countries, as well as data on drug purchases gathered separately by the World Health Organization, the analysis looks at prices paid in around 15,000 ARV procurements worth more than $1 billion that took place between 2002 and 2008.

Overall, two-thirds of the drugs procured were generic formulations. Although prices of generic and branded drugs fell over the six-year study period, analysis of year-by-year changes revealed some complex patterns.

In particular, price reductions tended to be smaller for protease inhibitors, and smaller for all branded products than for generic versions.

There were also big variations between countries in the prices paid for both generic and branded products, even within the same income bands. In middle-income countries for example the price of almost one in five branded antiretroviral products varied at least threefold between purchases, and in low-income countries the price of five generic products varied at least threefold in 2007-2008 alone.

Although the authors do not offer explanations for the extent of variation between purchases, they say that greater transparency about the prices being paid for antiretroviral drugs could assist countries in getting better value for money.

They also note that their analysis confirms the oft-repeated observation that countries pay less for most generic versions of antiretroviral drugs, although they note that generic versions of protease inhibitors remained more expensive, on average, than branded versions up to the end of 2008.

They suggest that low global demand for protease inhibitors, coupled with the wide range of possible products, may explain the higher prices paid for this class of drug. If procurement were to be consolidated around a much number of products in this class, prices might be driven down further, the authors speculate.

However, greater generic competition will also be needed to drive down prices, and the same is true for abacavir and tenofovir, which also remained expensive relative to other drugs of the nucleoside reverse transcriptase inhibitor class at the end of 2008.

Mechanisms such as the patent pool for ARVs being developed the international drug purchase fund UNITAID will also help to promote competition and drive down prices, the authors suggest.

Reference
Waning B et al. Temporal trends in generic and brand prices of antiretroviral medicines procured with donor funds in developing countries. Journal of Generic Medicines 7 (2): 159-175, 2010. (Full text article freely available here).

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If Started Early, HIV Treatment Reduces Death Rates toward Background Levels in African Countries. 2/5/10

Mortality among HIV-infected people during the first two years of ART is higher than in the general population in these four sub-Saharan countries

2 May 2010

Mortality rates of people starting HIV treatment in four African countries approach those of the general population over time, provided that treatment is started before the immune system has been severely damaged, according to new research.

In sub-Saharan Africa more than 2 million people with HIV now receive antiretroviral treatment (ART), and mortality in HIV-infected patients who have access to ART is declining. In the new study, Matthias Egger of the University of Berne and colleagues investigated how mortality among HIV-infected people starting ART compares with non-HIV related mortality in Cote d'Ivoire, Malawi, South Africa, and Zimbabwe.

The researchers analyzed information about people during their first two years on ART in five treatment programs participating in the International epidemiological Databases to Evaluate AIDS (IeDEA) initiative, and obtained estimates of HIV-unrelated deaths in these countries from the World Health Organization Global Burden of Disease (GBD) project.

Their findings indicate that mortality among HIV-infected people during the first two years of ART is higher than in the general population in these four sub-Saharan countries. However, for patients who start ART when they have a high CD4 lymphocyte count and no signs of advanced HIV disease, the excess mortality is moderate and similar to that associated with diabetes.

 This study was supported by the Office of AIDS Research (OAR) of the National Institutes of Health, the Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS), and the National Institute of Allergy and Infectious Diseases (NIAID, grant 1 U01 AI069924-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 

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Inflammation Associated with Increased Mortality Risk for Patients with HIV, Even when CD4 Cell Count High. 8/7/10

"Elevated levels of fibrinogen and CRP [C-reactive protein] were strong and independent predictors of 5-year mortality risk."

AIDSMap

By Michael Carter
6 July 2010

High levels of two markers of inflammation – fibrinogen and C-reactive protein – are independently associated with an increased risk of mortality for patients with HIV, even when they have a strong immune system, US investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

“We found that elevated levels of fibrinogen and CRP [C-reactive protein] were strong and independent predictors of 5-year mortality risk. Our findings suggest an important role for inflammation in mortality risk”, comment the investigators.

The study’s findings could help explain why, despite effective antiretroviral therapy, mortality rates remain higher amongst individuals with HIV than in the general population.

Only one earlier study (the SMART treatment interruption study) has found an association between inflammation and an increased risk of mortality for HIV-positive patients in the era of modern antiretroviral therapy. This research showed that there was a strong association between levels of the inflammatory markers D-dimer, Il-6, and C-reactive protein and mortality.

Separate research conducted by investigators from the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study group identified an association between HIV and elevated levels of fibrinogen, an inflammatory marker connected with clotting.

The FRAM investigators hypothesised that inflammation, indicated by elevated levels of fibrinogen and C-reactive protein, would be independently associated with an increased risk of death during five years of follow-up in their cohort of 922 patients.

The patients were stratified according to their baseline fibrinogen levels ( below 319 mg/ml; 319-406 mg/dl; and above 406 mg/dl), and according to their CD4 cell counts (below 200; 200-350; 350-500; and, above 500 cells/mm3).

Compared to individuals with lowest fibrinogen levels, those with fibrinogen above 406 mg/dl were significantly older (41 vs. 43years, p = 0.008), were more likely to be African American (29 vs. 50%, p = 0.018), to be using medication to control blood pressure (12 vs. 16%, p 0.012), to have higher total cholesterol p = 0.014) and lower HDL cholesterol (p = 0.041) and to have higher levels of C-reactive protein (p < 0.0001).

Over the five-year period of the study, individuals with the highest fibrinogen had a mortality rate of 25% compared to a rate of just 7% for those with the lowest fibrinogen levels.

Mortality rates also differed according to baseline levels of C-reactive protein. Individuals with a C-reactive protein level above 3 mg/dl had a mortality rate of 19% compared to a rate of 7% for those with C-reactive protein levels below 1 mg/dl.

Compared to individuals with fibrinogen below 319 mg/ml, those with the levels of this marker of inflammation had a three-fold increase in their mortality risk (OR = 3.35; 95% CI, 1.99-5.65, p < 0.001).

In addition, high levels of C-reactive protein were also significantly associated with an increased risk of death, the mortality risk being almost four-fold higher for those with a level above 3 mg/dl than those with C-reactive protein below 1 mg/dl (OR = 3.72; 95% CI, 2.09-6.63, p < 0.001).

When fibrinogen and C-reactive protein were included in a model together, high levels of both remained independently associated with an increased risk of death (fibrinogen, p = 0.001; C-reactive protein, p = 0.002).

Next the investigators examined the relationship between CD4 cell count, inflammation and mortality.

In every CD4 cell category, each 100 mg/dl increase in fibrinogen increased the risk of death (1.93 for those with a CD4 cell count below 200 cells/mm3; 1.30 for those with a CD4 cell count above 500 cells/mm3).

Even when the investigators adjusted their results for evidence of renal disease, higher levels of both markers were associated with an increased risk of mortality in each CD4 cell category.

“We conclude”, write the investigators, “that elevated levels of fibrinogen and CRP are strong and independent predictors of all-cause mortality in HIV-infected adults.”

They continue, “our findings that fibrinogen and CRP remained associated with higher odds of death regardless of the degree of immunosuppression suggests that inflammation remains an important factor even in those with relatively preserved CD4 cells.”

The investigators call for further research “to determine whether interventions to reduce fibrinogen and CRP levels might decrease mortality risk in HIV-infected adults.”

Reference

Tien PC et al. Inflammation and mortality in HIV-infected adults: analysis of the FRAM cohort study. J Acquir Immune Defic Syndr, advance online publication, July 2010.

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KENYA: Government takes First Steps to Roll out Less Toxic ARVs. 27/7/10

HIV-positive people on treatment will be switched from regimens containing the antiretroviral Stavudine to less toxic combinations

27 July 2010

Nairobi - HIV-positive people on treatment will be switched from regimens containing the antiretroviral Stavudine to less toxic combinations in line with UN World Health Organization (WHO) guidelines, according to a senior official.

"We want to start initiating patients to the safer drugs recommended by the WHO as soon as next month [August]," Ibrahim Mohamed, director of the National AIDS and Sexually transmitted infections Control Programme (NASCOP), told IRIN/PlusNews. "We will be communicating this to treatment facilities in the country; we are working [on] the guidelines which they will be given."

WHO has recommended that Stavudine be replaced with less toxic drugs such as Tenofovir (TDF) or Zidovudine, better known as AZT. Some of the side-effects of Stavudine include nerve damage and changes in body shape.

"We have sourced drugs and when they arrive, we will distribute them throughout the country once we issue guidelines to health professionals," Mohamed said.

Patients have greeted the news with cautious excitement. "People have been experiencing side-effects with Stavudine but you have to make a choice between living [with the side-effects] or refusing to take it and end your life," said Doreen Anjalo, who has been on ARVs for four-and-a-half years. "Our only worry is where the government will get the money."

Funding concerns

According to Mohamed, Anjalo is right to be concerned. Two consecutive rejections by the Global Fund to fight AIDS, Tuberculosis and Malaria mean the government may remain cash-strapped for a while and may be unable to roll out the new drugs quickly.

"Of course we are going to be gradual because we don't have much money to start implementing this at once - we expect to phase it [Stavudine] out completely by the end of four to five years."

At an estimated US$20 per person per year, Stavudine is significantly cheaper than Tenofovir, which costs $85, and Zidovudine, which costs $91 per person annually.

In addition to paying for more expensive drugs, the government has agreed to follow new WHO guidelines to treat people at a higher immunity level, or CD4 count, which will increase the numbers in treatment.

"You know we are expected to not only phase out the toxic drug but also to initiate patients [to] treatment earlier than before; the financial implications are there and we are grappling with that too," said Mohamed.

A budgetary allocation of $11.25 million for ARVs will only contribute a fraction of the cost of the additional treatment and new drugs. According to the Kenya National Strategic Plan for HIV/AIDS, the government faces a shortfall of nearly $1 billion to treat an estimated 500,000 people by the end of 2013; so far, some 300,000 Kenyans receive ARVs.

"We as the government must look for alternative sources of funding; there are various recommendations being pursued now, but we are also looking forward to getting money from the [next round of the] Global Fund," Mohamed said.

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Kenya: "R U OK 2day?" SMS Check-Up Takes Off. 1/4/10

Mobile phones help reduce cases of stigma because they create a sense of privacy

1 April 2010

NAIROBI/KAJIADO - Phoebe Mapelu's job as a community health worker in Kenya's Kajiado District always meant going from door to door - sometimes with long distances between homes - to check up on patients on life-prolonging antiretroviral therapy (ART).

"In a day, I can visit 15 people. It's hard because they stay far away from each other, but they need you," she told IRIN/PlusNews. "I am their bridge to the health facility or the doctor."

Mapelu's life has been made considerably easier by the growing use of mobile phone technology, even in rural areas like Kajiado. Even though she still has to make visits, she can track her patients more easily through calls and text messages.

Mobile phone use in Kenya has risen rapidly from 200,000 users in 2000 to an estimated 17.5 million today.

"Making a visit does not mean you will get them at home; they have work to do too, but since they started using these phones, I am now able to know whether a client is home or not," she said. "They are also able to call me if they want me before my scheduled visit."

Lightening the load

Sarah Karanja, study coordinator of the Weltel Project, an initiative to use mobile phones to improve health systems, says the use of mobile phones to track patients has taken a burden off health workers.

"Eighty percent of those [health workers] we talked to in Nairobi and Kajiado said they feel relieved - health workers need that kind of relief," she said. "Patients, on the other hand, feel they are cared for which is good for their health and wellbeing."

An ongoing Weltel study uses a weekly text message to study mobile-phone effectiveness for health; the message to the patient reads “Mambo”, Swahili for “how are you”, to which the patients can respond “Sawa”, OK, to show they are fine, or “Shida”, which means problem, to show they need attention.

Patients who respond Shida and non-responders are followed up with a call from the clinic nurse to identify and handle any problems.

Initial study findings reveal that 80 percent of patients are comfortable with the use of mobile phones to manage their HIV care and treatment.

"Now I don't have to wait... I can ask if she is coming or not," said Meshack, a patient in Kajiado. "When I leave home to attend to my business, I can let her know and I can tell her my problem anywhere."

Easing stigma

According to Daniel von Rege, field coordinator for the medical NGO Médecins San Frontières - which runs a large HIV programme in Kibera, a slum in the capital, Nairobi - the use of mobile phones leads to better follow-up of patients.

"Mobile phones help reduce cases of stigma because they create a sense of privacy," he said. "Health workers are known and some patients do not want them to visit their homes or go to the facility frequently because this will give away their status; when you give them a platform to interact with the facility without a physical visit, then you improve their stay within the care and treatment programme."

Cost issues

He noted that one drawback to the use of mobile phone technology was cost. "In Kibera, for e