April-June 2011, Volume 4, Issue 2
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Map of Ongoing HIV Prevention Research Trials
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Treatment as Prevention Studies Table (PDF,
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Tenofovir Gel Timeline (PDF,
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April-June 2011, Volume 4, Number
2
Contents:
- AVAC's Take
- Data Dispatch
- ARV-Based Prevention in HIV-Postiive Individuals: Relevant studies
- At a Glance
- Coming Soon
AVAC's Take
In a newly designed Px Wire centerspread, AVAC debuts a table of ongoing trials of ARV-based prevention in HIV- positive people. This broad category of research includes trials of the “test and treat” strategy that seeks to initiate ARV treatment in people as soon as they test HIV-positive, and other trials that seek a prevention benefit from starting individuals on ARV therapy at higher CD4 thresholds. One goal of these studies is to assess whether significantly decreasing levels of HIV viral load will reduce the rate of HIV transmission. These trials complement research on PrEP and ARV-based microbicides, which seek to use ARVs as prevention in HIV-negative people.
In the end, the goal remains universal access to AIDS treatment and prevention. AVAC hopes this table will be a tool to help bring the prevention and treatment threads in science and advocacy together into a single conversation and agenda for action.
Data Dispatch
The recent 18th Conference on Retroviruses and Opportunistic Infections (CROI) provided new findings on medical male circumcision. For AVAC’s ARV-based prevention roundup from CROI visit www.avac.org/prep. While CROI was kicking off, new AIDS vaccine data was published.
One of the key questions with any prevention strategy is how long the protection lasts and whether the level of protection changes over time. New long-term follow-up data from a male circumcision for HIV prevention trial in Rakai, Uganda, suggest that circumcision among HIV-negative men provides a durable risk-reduction benefit, which actually increases over time. The trial halted randomization in 2006 after it found that there were approximately 51 percent fewer HIV infections among men who received circumcision compared to those assigned to the control arm.
At CROI, Xiangrong Kong of Johns Hopkins University presented data on HIV rates among men from the circumcision arm of the trial nearly five years after randomization was halted. HIV rates in this group were 73 percent lower than in men from the control group who chose to remain uncircumcised. She also noted that men from the control group who opted for circumcision when randomization ended had a 67 percent reduction in HIV infections compared to the uncircumcised cohort.
The follow-up Rakai data also show no increase in the number of non-marital partners reported by participants. However, the researchers found that men in both the control group and the circumcised group reported reductions in condom use during follow-up. Study authors suggest that this change in behavior might be related to the fact that participants stopped receiving intensive risk-behavior counseling once the randomized trial was completed.
Over three years after immunizations were stopped in the Step AIDS vaccine trial, the study is still yielding scientific clues. An article in Nature Medicine (17, 366- 371, 27 February 2011) described the analyses of viruses obtained from volunteers who received either the vaccine strategy or the placebo but later became HIV-positive. The researchers analyzed viral strains from participants in both arms and found differences in the viral genetics of strains from vaccine recipients. They concluded that vaccine-induced T-cell responses had influenced the genetic make-up of the virus with what is known as a “sieve effect”. This term is used to describe what happens when immune responses successfully inhibit some virus variants from replicating but not others.
These are the first data to show that a T cell-based vaccine tested in humans can have an impact on the genetic make-up of the virus. Researchers are conducting analyses of viruses isolated from participants who acquired HIV in the Thai trial (RV144) and are looking for similar effects.
ARV-Based Prevention in HIV-Positive Individuals: Relevant studies
Today there are several trials evaluating the use of ARV-based prevention in people with HIV. The goal of these “treatment as prevention” strategies is to reduce viral load and thereby reduce individuals’ infectiousness. Data gathered from serodiscordant couples enrolled in a trial of HSV-2 treatment for HIV prevention showed that effective ARV treatment reduced HIV transmission by approximately 92 percent. These data were not from a randomized controlled trial and ongoing trials—many listed below—will provide additional information. Not included in this table are the many ecological studies of ART impact on HIV prevalence in different settings.
At a Glance
Planning Ahead for Trial Success
In January in Johannesburg, AVAC partnered with the Microbicide Trials Network (MTN), Southern African AIDS Trust and the Treatment Action Campaign to organize “Next Steps for ARV-based Prevention”, a civil society consultation on follow-up research with a focus on what may come after the VOICE trial. (VOICE is evaluating daily TDF, daily TDF/FTC and daily 1% tenofovir gel.) Given the recent results of the CAPRISA 004 microbicide and iPrEx PrEP trials, it is critical to continue to prepare for potential positive results from other ongoing trials of oral and topical ARV-based formulations.
Part of the civil society consultation was allocated to discussions of MTN 018, or CHOICE, a planned follow-on trial that would be initiated if one or more of the strategies being evaluated in the VOICE trial were found to be safe and effective. The forty advocates from East and Southern Africa discussed the proposed MTN 018 trial design as well as the regulatory process for approving the gel should it show effectiveness in VOICE—results are expected in early 2013. (The same gel candidate used in VOICE showed 39 percent protection against HIV in the CAPRISA 004 trial but used a different dosing strategy.) Following this community consultation, the MTN 018 Protocol Development Team met and incorporated the civil society feedback into its deliberations. Engaging civil society while the trial protocol is in development is an example of good participatory practice guidelines in action (see “Coming Soon”).
Future Directions for HIV Research
The US National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH), is in the process of restructuring its $300 million HIV/ AIDS clinical trials networks. The awards supporting the six current HIV/AIDS networks are set to expire in 2013 and 2014. A primary aim for the next funding cycle (2013–2020) is to broaden the networks’ scope by establishing multi-disease research capacity on the existing infrastructure of the HIV/AIDS trials network. This expansion would accommodate the study of tuberculosis, hepatitis and other HIV comorbidities.
The four priority areas for the newly named “NIAID HIV/AIDS and Infectious Diseases Clinical Trials Network” are HIV Prevention, HIV Vaccines, Therapeutics, and Pediatric and Maternal & Child Health. Funding for the HIV Prevention Network will be divided into two groups: Microbicides and Integrated Prevention Strategies (including PrEP and ARV-based prevention in HIV-positive people). An additional priority area will be funded for non-HIV/AIDS infectious disease research.
Splitting microbicides and PrEP into separate groups could raise questions about leadership of the scientific agenda going forward, since both fields are focusing on ARV-based prevention. AVAC and other advocacy groups have raised this in feedback on the restructuring process and call on NIAID to ensure that there are strong governance structures that support cross-network communication and collaboration.
NIAID is soliciting input into the restructuring process here
Coming Soon
In April, UNAIDS and AVAC are planning to release the second edition of the Good Participatory Practice guidelines for biomedical HIV prevention trials. The GPP guidelines provide funders, sponsors and implementers with systematic guidance on how to engage with stakeholders in the design and conduct of biomedical HIV prevention trials. Since 2007, the GPP guidelines have been applied in different settings and were the subject of formal global consultations. The guidelines will be available for download at www.avac.org/gpp—printed copies can also be requested.