Susan Buchbinder, MD, and Albert Liu, MD, discuss the promising results from their recent study of ARVs for HIV prevention in high-risk populations.
As we approach the 30-year anniversary of the first reported AIDS cases, we are beginning to realize the potential of using antiretroviral agents for HIV prevention. Since the mid-1990s, we've known that antiretrovirals can be highly effective in reducing mother-to-child transmission, and we've surmised (although not proven definitively) that antiretrovirals can prevent HIV acquisition when given as postexposure prophylaxis (PEP). In 2010, a pair of studies demonstrated that tenofovir (TDF)-based regimens can protect against sexually acquired HIV infection. First, the CAPRISA 004 study showed a statistically significant 39% reduction in HIV acquisition among women who were given TDF vaginal gel to be administered before and after vaginal intercourse. Then, in November 2010, we reported results from the iPrEx study, the first-ever biomedical prevention strategy to reduce HIV acquisition among men who have sex with men (MSM) and transgender women who have sex with men. We enrolled 2,499 MSM and transgender women from 6 countries in North and South America, Africa, and Asia, and randomly assigned participants to receive a daily combination pill of TDF disoproxil fumarate/emtricitabine (TDF/FTC, or Truvada), a strategy known as preexposure prophylaxis (PrEP), or a placebo pill. Participants assigned to receive TDF/FTC had a 44% lower risk of HIV acquisition compared with those receiving placebo pills. In both studies, rates of adherence to the study regimen appeared to correlate with efficacy. In the iPrEx study, a preliminary analysis suggested that efficacy could be as high as 92% among men with detectable levels of TDF/FTC compared with those without detectable levels of the drug in the blood.
In response to these promising results, the CDC issued sound interim guidelines for oral PrEP on January 27, 2011. Although plans are under way to convene an expert panel and to seek public input to develop recommendations for oral PrEP use, the CDC wanted to ensure that PrEP was not misused in the interim, as TDF/FTC is a licensed drug in the United States, and could be prescribed for or acquired by HIV-uninfected persons. PrEP has been demonstrated to provide protection only for MSM who take daily TDF/FTC, in the context of a comprehensive prevention package and with close medical and behavioral monitoring. Other trials will provide additional data for heterosexual men and women and injection drug users, other drugs, and other regimens. Until these data are available, alternative strategies should not be tried. Close medical monitoring, particularly HIV testing, is imperative, as resistance develops quickly if PrEP is initiated (or perhaps reinitiated) when a patient is already HIV infected. Finally, there is not yet any substitute for condoms. Efficacy was partial, and although there is promise that, with improved adherence, there will be higher efficacy, that has yet to be demonstrated. Further PrEP recommendations will take into account a full review of the data, including longer-term data from iPrEx. Many other scientific, operational, and financial questions must be addressed, to ensure that PrEP is used most effectively for patients who will benefit most.
Thirty years into the epidemic, we have cause for optimism. But our best hopes for ending the epidemic ultimately revolve around the development of a safe and efficacious preventative vaccine.
- Grant RM, Lama JR, Anderson PL, et al; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30;363(27):2587-99.
- Sokal D, Karim Q, Omar Z, et al. Safety of 1% tenofovir vaginal microbicide gel in South African women: results of the CAPRISA 004 trial. In: Program and abstracts of the XVIII International AIDS Conference; July 18-23, 2010; Vienna. Abstract TUSS0504.