What’s up with the HIV clinical trials networks

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Center Scientific Advisory Committee member Sten Vermund, MD, PhD

Leaders of several HIV clinical trial networks shared information about the respective missions and agendas of these vital research consortia in one of the opening sessions at the Infectious Diseases Society of America 49th Annual Meeting.

Daniel Kuritzkes, MD, principal investigator of the AIDS Clinical Trails Network (ACTG) defined the mission of the ACTG – with its 34 domestic and 18 AIDS Clinical Trial Units – to reduce the global burden of HIV through therapeutic research.  There are 75 clinical research sites in the ACTG and their research has helped to define optimal clinical care for HIV throughout the world.  Kuritzkes highlighted the future areas of emphasis for the ACTG—tuberculosis, viral reservoirs and HIV eradication, inflammation and end organ disease and viral hepatitis.

Sten Vermund, MD, PhD, principal investigator of the HIV Prevention Trials Network (HPTN), described the now widely reported results of HPTN 052, which demonstrated a 96 percent reduction in the risk of transmission to the uninfected sexual partner in a discordant couple when the HIV infected partner is virally suppressed with antiretroviral therapy (ART).  He highlighted several of the family of studies that have been generated by these landmark clinical trial results

One of those studies – Project Accept or HPTN 043 – is a community-based randomized study intervention to increase HIV testing and case detection in persons aged 16-32 in Tanzania, Zimbabwe and Thailand to evaluate whether increasing testing can reduce HIV incidence. Although ongoing, the study has already made it clear that testing rates can be dramatically increased: In Tanzania, 37 percent of persons have tested for the first time in the intervention community compared to 9 percent in the control community; In Zimbabwe, 51 percent of persons tested for the first time in the intervention compared to 5 percent in the control community. Much of the HIV testing conducted in the intervention communities was done through the use of mobile vans.

Vermund also flagged the PopART study- one of three major combination prevention trials being funded through the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), the National Institutes of Health and the Bill & Melinda Gates Foundation.  The goal of this study – and two others funded through the Centers for Disease Control and Prevention and the U.S. Agency for International Development – is to identify combination interventions that reduce HIV incidence, overall morbidity and mortality, and that are sustainable. This study will be conducted in target communities in Zambia and the Western Cape of South Africa.

Ian McGowan, MD, PhD, one of the principal investigators of the Microbicide Trials Network, highlighted some of the work of this important network with its emphasis on oral and topical pre-exposure prophylaxis (PrEP) using antiretroviral drugs.  He spoke about the Vaginal and Oral Interventions to Control the Epidemic (VOICE) study and some of the myriad analyses that are being done in association with the trial.  While the Data Safety and Monitoring Board (DSMB) stopped the oral tenofovir study arm because it would not be able to demonstrate effectiveness, the study continues. In addition to evaluating oral Truvada and antiretroviral topical gel and their effectiveness in preventing HIV acquisition, VOICE is also looking at drug resistance, the impact of the antiretroviral medications on the bone health of HIV uninfected women, studying community perceptions of the clinical trial and conducting a special study of the women who acquire HIV during the trial. VOICE is also conducting safety studies of the drugs and the gel in pregnant women, given the risk of HIV acquisition and transmission during pregnancy.  Most of the approved antiretroviral drugs have not been tested in pregnant women.

McGowan also noted the continuing work on the development of a rectal microbicide, a very important potential HIV prevention tool for men and women in the developed and the developing world. Notably, 15 to 20 percent of the women in the VOICE trial reported having engaged in receptive anal intercourse in the last three months.  Of course, a rectal microbicide is a critical tool for men who have sex with men who dominate the HIV epidemic in most developed countries and are at extremely high risk for HIV infection in the developing world as well. He flagged the MTN 017 study as an important Phase II rectal microbicide trial underway in the U.S., Thailand, Peru and South Africa, and noted that the next major clinical trial of a microbicide for women is ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) which will test a daprivirine vaginal ring in 3,500 women.

McGowan acknowledged that there is a way to go before operationalizing PrEP given the negative results of the FemPREP trial and the tenofovir oral arm of VOICE. He noted many challenges including bridging the end of PrEP effectiveness trials with the community availability of PrEP agents.

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