Network News • October 2011 • Issue No. 6
What's New in the HPTN?
New Combination HIV Prevention Strategy Study
HPTN 071 is a natural extension of HPTN’s robust HIV prevention research and will build upon the network’s groundbreaking studies. The primary objective of HPTN 071 is to evaluate a prevention package utilizing a combination of interventions including voluntary testing, counseling and antiretroviral therapy (ART). The study is in line with the goals of the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) which aims to “expand its emphasis on HIV prevention, and matching interventions and investments with epidemiological trends and needs in order to improve impact.”
Data from recent clinical trials have been helpful in determining the impact of HIV prevention strategies at the individual level (e.g., use of antiretroviral drugs (ARVs) for prevention of infection in men and women, use of topical ARVs for prevention of HIV infection in women, male circumcision). Earlier this year two large scale HPTN studies showed impressive results which have helped to propel HIV prevention research. Project Accept (HPTN 043) was a randomized study that found that adding community mobilization and support services to a mobile HIV counseling and testing program can improve rates of testing in rural communities. HPTN 052 was the first randomized trial to show that treating an HIV-infected individual with ART can reduce the risk of sexual transmission of HIV to an uninfected partner. After evaluating the components of testing and treatment separately, HPTN 065 is designed to evaluate a combination of prevention strategies. Known as TLC-Plus (Test, Link to Care, Plus Treatment), this study will evaluate the impact of expanded HIV testing, linkage to care, viral suppression through adherence to ART, prevention for positives through risk-reduction counseling, and patient and provider surveys.
Starting in 2012, HPTN 071 will be carried out in 24 communities in Zambia and South Africa. Eight communities will receive the full PopART intervention, while eight communities will receive current standard of care. The remaining eight communities will receive an intermediate intervention which includes all the components of PopART but adheres to current ART national guidelines. A total of 60,000 adults will be followed for two years to measure the impact of these interventions on the rate of new HIV infections.
HPTN 071 will evaluate the impact of HIV prevention combinations at the population level. This study will provide important data on how best to combine interventions for HIV prevention in different populations and settings to optimize the reduction in HIV incidence. The study will also provide evidence as to which combinations of interventions, doses and levels of coverage are optimal for decreasing HIV transmission, including data on cost-effectiveness.
The HPTN is excited to add the 071 study to its scientific portfolio. It represents another important step in developing and implementing combination prevention strategies that demonstrate a significant and measurable reduction in HIV incidence in populations that bear a disproportionate burden of HIV infection.
The HPTN 071 study was selected after two sequential and systematic peer reviews of proposals. The solicitation, Evaluation of the effectiveness of combination HIV prevention interventions for generalized HIV epidemics in countries receiving PEPFAR support, was made available under Cooperative Agreement UM1 AI068619, funded by the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Mental Health, (NIMH). This specific award was underwritten by the Office of the United States Global AIDS Coordinator (OGAC) with substantial additional support from that National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation (BMGF).
HPTN 058 Study Closes
An independent Data Safety and Monitoring Board (DSMB) met on September 27, 2011 and determined there was insufficient evidence to adequately answer the primary objectives of the study. As a result, HPTN 058 ended enrollment of new participants. Because the DSMB identified no safety concerns, current participants will be gradually rolled off the study in an orderly and safe fashion.
The HPTN 058 study was conducted by a team of researchers located in Thailand, China, and the United States. The study was designed to determine whether Long-term (52 weeks) Medication-Assisted Treatment with buprenorphine/naloxone and a behavioral intervention for opiate-dependent participants would achieve a long term reduction (that is, when evaluated at 104 Weeks after enrollment) in cumulative HIV incidence and death compared to Short-Term (~ 3 weeks) Medication-Assisted Treatment with buprenorphine/naloxone and the same behavioral intervention. Approximately 1,250 participants were enrolled at sites in Thailand and China. After analyzing the data currently available, the DSMB determined that the study would not be able to demonstrate a difference between the two treatment groups. However, the study will be able to address a number of important secondary objectives. Analysis of data from HPTN 058 will provide much needed new information on promising approaches for HIV prevention among injection drug users.
What's New in Prevention?
Let's Talk about PrEP
In September, the Microbicides Trial Network (MTN) announced that its HIV-prevention study, VOICE, (Vaginal and Oral Interventions to Control the Epidemic), would be modified and the daily oral dose of Tenofovir disoproxil fumarate (TDF) in one arm would be discontinued. This decision followed an independent Data Safety and Monitoring Board (DSMB) review which determined that the trial would not be able to demonstrate that tenofovir tablets (TDF) used orally are effective in preventing HIV in the women enrolled in the trial. The arms of the study that are testing Truvada® and the vaginal gel form of tenofovir are continuing.
The VOICE study modification comes on the heels of two studies with promising PrEP results. In July, the TDF2 study sponsored by the United States Centers for Disease Control and Prevention (CDC), provided evidence that HIV infection among heterosexuals can be prevented by taking a daily oral dose of Truvada®, a formulation that is a combination of tenofovir and emtricitabine (TDF/FTC). In TDF2, study participants in Botswana were given either a placebo or a daily, oral dose of Truvada. Using an intent-to-treat analysis the study found Truvada reduced HIV acquisition by 63%.
A second study, Partners PrEP, sponsored by the Bill and Melinda Gates Foundation, and conducted in Kenya and Uganda, was a three arm trial evaluating a daily oral dose of tenofovir (TDF), or a daily oral dose of Truvada® against a placebo. The study found that both regimens were effective in reducing HIV acquisition for men and women: 62% efficacy for tenofovir (TDF) and 73% efficacy for Truvada (TDF/FTC).
“Given the positive results from the Partners PrEP study that compared daily oral tenofovir to Truvada® in discordant couples and established safety and efficacy with both products, the rationale for the DSMB recommendation to stop the tenofovir arm of the VOICE study for futility awaits further analysis from this arm of the VOICE study,” says Quarraisha Abdool Karim, co-principal investigator of the HPTN, and lead author of the CAPRISA 004 tenofovir microbicide trial. “We need to further analyze and compare data from completed trials with oral and topical formulations of anti-retrovirals to better understand why we have observed efficacy in some instances and not in others.”
VOICE is the second PrEP study to be modified this year. In April, FEM-PrEP stopped its Phase III, randomized, placebo-controlled clinical trial of a daily oral dose of Truvada® for HIV prevention among women in sub-Sahara Africa, following the trial’s Independent Data Monitoring Committee’s determination that it would be unlikely to demonstrate Truvada’s effectiveness in preventing HIV infection in the study population.
Dr. Sten Vermund, principal investigator of the HIV Prevention Trials Network, and Amos Christie Chair of Global Health at Vanderbilt University School of Medicine says, “In light of the Partners PrEP and CDC TDF2 HIV prevention studies which have shown strong evidence that PrEP can provide protection against HIV acquisition in women, it is disappointing that oral tenofovir did not reduce HIV infection in VOICE study participants. We need to be resolute in our scientific endeavors to understand these disparate results and look closely at the issue of adherence to prophylactic medications.“
HPTN 052 Highlighted at IAS Conference in Rome, Italy
The study found that in HIV serodiscordant couples, in which one person is infected with HIV and the other is not, providing early antiretroviral therapy to the HIV infected person reduced sexual transmission of HIV to the uninfected partner by 96%.
Along with the special symposium for 052, the HPTN was well represented at IAS with six oral presentations and three exhibit posters. A summary report of HPTN at IAS includes links to oral presentations at the conference, 052 video press conference excerpts, as well as links to various documents highlighting HPTN's research.
In the Community
New Community Working Group Co-Chair
“We are delighted to have Melissa in this leadership role,” says Janet Frohlich, Chair of the HPTN Community Working Group. “She has established working relationships with key stakeholders and brings a wealth of understanding to HIV prevention science as well as insight and experience in providing direct care to at-risk populations.”
Melissa began working with the HPTN in 2007 and has been actively involved in HPTN 061, HPTN 064, and serves on the protocol team for HPTN 065. “I am excited to take on the challenges of this position,” says Turner. “I am especially committed to identifying creative and effective solutions to bridge the divide that exists between HIV science and the community at-large.”
Deciding Moments Campaign
Deciding moments are opportunities to take a stand against HIV and be “greater than” the disease. The campaign encourages people to be agents for change; to make a commitment to get tested, correct misinformation about HIV/AIDS, and keep up with medications. The central idea behind Greater than AIDS is that through the power of individuals acting together, they can achieve a greater goal and collectively change the course of the epidemic.
A series of public service ads was inspired by Greater than AIDS. It features true stories from people across the United States, including those living with HIV, who share their own deciding moments in the hope of inspiring others to join the effort to take a stand against HIV and help stop the spread of the disease.
A Closer Look
Project SOS (Saving OurSelves)
Even though Black men who have sex with men (Black MSM) make up less than half of one percent of the U.S. population, CDC data show that in 2009 they accounted for more than 20% of new HIV infections. “These rates of infection are astounding,” says Perkins. “A lot of attention has been paid internationally to high levels of HIV in areas like sub-Saharan Africa, but this allows us to take a closer look at the problem in our own backyard.”
HPTN 061 hopes to gain a better understanding of Black MSM and their lives, risks, attitudes and how the men might be affected by their religious experiences, or perceptions of racism and experience of homophobia, or sexual abuse while a child.
The Project SOS study is designed to evaluate new approaches to reduce HIV risk in Black MSM through a multi-pronged approach:
Perkins believes HIV prevention work is about social justice, equal access to care and treating people with dignity and respect. He says Project SOS is a great example of the importance of community buy-in and assembling a strong study team. He jokingly refers to his team as the “SOS Band”. “This is an amazing group of guys who are passionate about the community and really believe in this work. I am extremely proud of all of them.”