This week’s New England Journal of Medicine showcases the results of clinical trials testing the use of antiretroviral drugs to prevent HIV acquisition in uninfected individuals. The results, which have been widely reported at major conferences, are mixed.
An article by Lut Van Damme and colleagues reports on the primary results of the Preexposure Prophylaxis Trial for HIV Prevention among African Women (FEM-Pr-EP)—a placebo-controlled trial of a once-daily oral two-drug combination among high-risk women in Africa. The trial was stopped early, in April 2011, when no effective preventive advantage was seen among those assigned to the drug combination , with low adherence identified as a major reason for the trial failure. The results of the “Partners PrEP study” of preexposure prophylaxis among HIV-serodiscordant heterosexual couples from Kenya and Uganda were more promising as reported by J.M. Baeten and colleagues in the same issue. They reported a relative reduction of 67 percent in the incidence of HIV in uninfected partners taking a single antiretroviral agent, and a 75 percent reduction in uninfected partners taking a two-drug combination. A third study funded by the CDC in Botswana, as reported by Michael Thigpen and colleagues, also reported signs of effectiveness from a trial of HIV uninfected men and women who were randomized to placebo or a two-drug combination. The study found a 62 percent reduction in the risk of HIV acquisition among those taking the antiretroviral combination.
The study articles and an accompanying editorial also note that another major PrEP clinical trial—the VOICE Trial—has discontinued the oral PrEP arm of two drugs—because of lack of efficacy. The provocative editorial authored by Myron Cohen and Lindsey Baden—“Preexposure Prophylaxis for HIV — Where Do We Go from Here?” calls for “additional studies to allow a proper understanding of the potential efficacy of and adverse events associated with preexposure prophylaxis and to identify other factors that might influence efficacy” while pursuing the “development of new prevention strategies as well as the deployment of all existing strategies, including the use of condoms, male circumcision, and the treatment of HIV-infected partners.” According to the authors, “further research is needed to identify the highest-risk populations and time period(s), and the preferred dosing strategy (daily or less frequent)” They also suggest the need to “better define the medical risks of the long-term use of these agents in a healthy population, to determine the costs, and to understand the effect on the induction and amplification of antiretroviral resistance in the patient and the community.” Healthcare providers who recommend preventive, pre-exposure use of antiretroviral drugs, the editorial concludes, will need to know the answers to those questions.