Results from three big HIV prevention trials were presented in one of the key sessions at CROI 2015.
The French-Canadian IPERGAY study evaluated "on-demand" PrEP, which consisted of two pills of tenofovir/emtricitabine (Truvada), two to 24 hours prior to sex, one pill 24 hours later, and a final pill at 48 hours. The study included 414 men or transgender women who have sex with men; at enrollment, participants indicated an average of eight sex partners in the previous two months, and 70% reported condomless anal sex. During a mean follow-up of 13 months, only 16 participants became HIV positive. The strategy demonstrated an 86% relative reduction in the incidence of HIV infection (P = .002). Of interest, the incidence of HIV infection in the placebo arm was 6.6 per 100 PY (person-years), and the number needed to treat to prevent one HIV infection was 18.
The PROUD study in England randomized 545 men who have sex with men to receive immediate PrEP with tenofovir/emtricitabine (n = 276) or "deferred" PrEP (initiating the strategy 12 months later). Subjects had a high risk for HIV infection, with 53% reporting any sexually transmitted infection, about 70% overall using recreational drugs, and 31% receiving any post-exposure prophylaxis (PEP) during the study. Results were similar to IPERGAY, with an 86% relative reduction in the incidence of HIV infection (P = .0002). The incidence of HIV infection in the control arm was 8.9 per 100 PY and therefore the number needed to treat was even lower at 13.
We ponder the need of exposing additional high-risk subjects to placebo in both studies years after the iPREX study results (demonstrating efficacy of the strategy and the close correlation with adherence) were published in the New England Journal of Medicine on Nov. 23, 2010, and presented at the 2011 IAS Conference in Rome. Of interest and not surprisingly, the DSMB committees of both studies stopped them, Oct. 10, 2014 in the PROUD study, and one week later in IPERGAY.
The PARTNERS study presented the third case of successful results for PrEP, this time in 1013 serodiscordant heterosexual couples in Uganda and Kenya. The strategy consisted of administering antiretroviral therapy to the positive partner, along with PrEP for the HIV-negative partner, during the first six months of treatment. If the positive partner did not receive or delayed the start of antiretroviral therapy, the negative partner maintained PrEP until the first six months of treatment. To date, a total of 858 person-years have been accrued. Here, the comparator risk was obtained from historical controls from the previous PARTNERS study, and was set at 5.2% infections. The strategy obtained a 96% risk reduction (P < .0001). Only two individuals were infected. In both cases, the positive partner did not receive antiretroviral therapy, and there were adherence issues in the negative partner. So, the brave title of the authors, "Near Elimination of HIV Transmission With a Strategy Combining PrEP and ART in Serodiscordant Couples," was justified.
Which other studies presented at CROI 2015 will have lasting impact? Read more of Llibre and Young's top picks.
Josep M. Llibre, M.D., is in the HIV Unit of the "Lluita contra la SIDA" Foundation at University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. Llibre has received funding for research or payment for conferences or participation on advisory boards from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare.
Benjamin Young, M.D., Ph.D., is senior vice president and chief medical officer of the International Association of Providers of AIDS Care based in Washington, D.C., and an adjunct professor at the Josef Korbel School of International Studies at the University of Denver. Young has received consulting or speaking fees from Bristol-Myers Squibb, Gilead Sciences, Merck & Co., and ViiV Healthcare. He has received research funding from Bristol-Myers Squibb Company, Gilead Sciences, Merck & Co., and ViiV Healthcare.