Network News • June 2011 • Issue No. 5
A Historic Time for the HPTN
Within the span of about a week, two large-scale HPTN studies have reported impressive results that will help propel the field of HIV prevention research forward.
HPTN 052 was the first randomized clinical trial to show that treating an HIV-infected individual with antiretroviral therapy (ART) can reduce the risk of sexual transmission of HIV to an uninfected partner. And just a week earlier, in the journal The Lancet Infectious Diseases, the National Institute of Mental Health (NIMH) Project Accept (HPTN 043) reported that adding community mobilization and support services to a mobile HIV counseling and testing program can improve rates of testing in rural communities.
Antiretrovirals for treatment and prevention
"The study was designed to evaluate the benefit to the sexual partner as well as the benefit to the HIV-infected person," says Dr. Myron "Mike" Cohen, the principal investigator of HPTN 052 and director of the Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill.
Results showed that when compared with starting ART at lower cell counts, initiating ART when cell counts were between 350 and 550 cells/mm3 reduced the risk of HIV transmission by 96 percent—a remarkable benefit for uninfected individuals. Early use also significantly reduced the risk of extrapulmonary tuberculosis, demonstrating an added health benefit for HIV-infected participants.
Increasing testing rates
The community-based testing intervention included mobile HIV testing along with both community mobilization and post-test psychosocial support services. The interim results of the study showed that the proportion of people who received their first HIV test during the study was higher in areas that received the "combination" testing than in those areas that received only clinic-based testing. Repeat testing also increased in the combination-testing areas throughout the trial. Further results, including how the intervention affects the rate of new HIV infections, will be available in 2012.
"Project Accept is an important demonstration that effective strategies, such as we developed and implemented, can encourage HIV testing and identification of persons with HIV and referral into care," said Dr. Thomas Coates, the protocol chair of the study and the director of the AIDS Institute at the University of California, Los Angeles.
Also known as TLC-Plus—short for test, link to care, plus treat—HPTN 065 is testing the community-level impact of implementing five synergistic study components: 1) expanded HIV testing, 2) linkage to care, 3) viral suppression through adherence to ART, 4) prevention for positives through risk-reduction counseling, and 5) patient and provider surveys. The HPTN, the U.S. Centers for Disease Control and Prevention, and state and municipal health departments are collaborating on the study, which is expected to last approximately three years.
What Else Is New in the HPTN?
HPTN a Leader in Treatment as Prevention
In early May, HIV/AIDS researchers from around the world convened to discuss the state of "treatment for prevention" at the three-day International Treatment for Prevention Workshop in Vancouver. HPTN 065 Principal Investigator Dr. Wafaa El-Sadr represented the HPTN at the international event, which was hosted by the British Columbia Centre for Excellence in HIV/AIDS.
"For a decade or more, there has been a lot of interest in treatment for prevention, mostly through modeling studies," Dr. El-Sadr said during the workshop.
While presenting an overview of scientific evidence supporting antiretroviral therapy (ART) as an HIV prevention strategy, Dr. El-Sadr also discussed observational studies and clinical trials of treatment for prevention, the risks and benefits of early ART for people living with HIV, gaps in knowledge, challenges for implementation, and ways to move the research forward.
"Now there is a need for population-level studies to determine the feasibility and the effectiveness of ART as a prevention intervention," she said. "HPTN 065 is under way to address this question, other feasibility studies are being developed, and more studies need to be planned urgently."
The workshop was co-hosted by the International AIDS Society, the Joint United Nations Programme on HIV/AIDS, the World Health Organization, and the National Institute on Drug Abuse. Access the agenda, webcasts, and more information here.
New HPTN Study to Be Decided Soon
On behalf of the National Institute of Allergy and Infectious Diseases (NIAID), the Office of the United States Global AIDS Coordinator, and the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the HPTN solicited and is now reviewing proposals for a new study to test the effectiveness of a combination HIV prevention strategy.
The new study will evaluate the impact of a combination prevention strategy on HIV incidence in countries that are supported by PEPFAR programs. It will also need to assess the population-level coverage of the proposed interventions and estimate the cost per HIV infection averted by the prevention strategy. A decision is expected in the coming months about which proposed study will become part of the HPTN's distinguished scientific portfolio.
What's New in Prevention?
Results from the FEM-PrEP Study
An independent data monitoring committee recently advised that it would be highly unlikely that the USAID-funded FEM-PrEP clinical trial would be able to demonstrate the effectiveness of Truvada (a combination of tenofovir disoproxil fumarate and emtricitabine) in preventing HIV infection in the study population, even if it continued to its originally planned conclusion.
The Phase III trial—implemented by FHI in partnership with research centers in three African countries—was designed to study whether HIV-negative women who are at higher risk of being exposed to HIV can safely use a daily dose of Truvada to prevent infection.
The FEM-PrEP outcome is surprising and disappointing, given a number of earlier studies suggesting the promise of pre-exposure prophylaxis (PrEP). However, as the FEM-PrEP trial undergoes an orderly closure, additional studies continue to evaluate the safety and effectiveness of a variety of PrEP regimens. Final analyses of the FEM-PrEP data will be conducted when the trial is completed, and primary results will be shared toward the end of this year.
The HPTN has three trials in development or in the field. These trials have different designs and are recruiting in different study populations than the FEM-PrEP trial.
HPTN Trials of Pre-Exposure Prophylaxis
In the Community
HPTN 052 Results Reach Communities Around the World
Results of the landmark HPTN 052 trial are being celebrated as an HIV prevention breakthrough by news media around the world. At least 337 unique media outlets in 32 countries have run stories mentioning both the trial and the HPTN. Many others are likely spreading the good news that early treatment with antiretroviral drugs can help prevent HIV transmission within serodiscordant couples.
HPTN leadership including Dr. Sten Vermund, Dr. Quarraisha Abdool Karim, Dr. Wafaa El-Sadr, and HPTN 052 Principal Investigator Dr. Myron "Mike" Cohen are among those who have been interviewed by the media. Read selected coverage of the trial at allAfrica.com, the British Medical Journal, The Lancet, the New York Times, and the Times of India.
A Closer Look
Commemorating 30 Years of AIDS
Just three decades ago, the virus causing AIDS had not been identified or named, and scientists and medical doctors were struggling to understand what was happening inside the bodies of patients who were infected. Flash forward 30 years, and remarkable achievements have been made in the identification, treatment, and prevention of the silent enemy we now know as HIV.
The first cases of AIDS were published on June 5, 1981, in the U.S. Centers for Disease Control and Prevention's Morbidity and Mortality Weekly Report. Over the next year, the National Institutes of Health (NIH) saw its first AIDS patients. Dr. Anthony Fauci, who now directs the National Institute of Allergy and Infectious Diseases (NIAID), was there from the beginning.
"It's totally transforming. Probably the best way to describe it to people is that when I began admitting patients, the median survival of those individuals was 26 weeks," says Dr. Fauci. But today, if a 20-year-old with HIV begins antiretroviral therapy in time, and gets the correct medicines, he or she could live an additional 50 years.
Great strides have also been made in HIV prevention, particularly in recent months. The Centre for the AIDS Programme of Research in South Africa (CAPRISA) showed that 1% tenofovir formulated as a microbicide gel could reduce a woman's risk of acquiring HIV. The iPrEX team provided the first evidence that pre-exposure prophylaxis (PrEP) with oral antiretroviral drugs could help prevent HIV infection. And the FEM-PrEP results have reminded us that there is no room for complacency in science.
Most recently, the National Institute of Mental Health (NIMH) Project Accept (HPTN 043) showed that community mobilization can boost HIV testing rates in remote areas, and HPTN 052 demonstrated that treating an HIV-infected person with antiretroviral therapy can dramatically reduce the risk of sexual transmission to an uninfected partner. The HPTN 052 data have expanded an already robust HIV prevention toolbox, significantly breaking down the false dichotomy between treatment and prevention. So where do we go from here?
"To fully realize the public health potential of advances in treatment and prevention, more efforts will need to focus on scaling up what we know works, in ways that are appropriate for different epidemic settings and that demonstrate impact at a population level," says Dr. Quarraisha Abdool Karim, co-principal investigator of the HPTN and associate scientific director of CAPRISA. "At the same time, we need to continue our efforts to find a vaccine, test novel strategies for preventing new infections, and expand HIV prevention options for women."