Background: Postexposure prophylaxis against potential human immunodeficiency virus (HIV) exposure has several limitations. Patients must not only recognize when they have been exposed to HIV, but they must also start therapy within 72 hours. Recently, HIV preexposure prophylaxis has gained increasing interest, particularly after one trial reported a 39 percent reduction in HIV infection rates among women who regularly used tenofovir 1% vaginal gel. The Preexposure Prophylaxis Initiative trial evaluated the safety and effectiveness of a combination of antiretroviral drugs for the prevention of HIV transmission.

The Study: A total of 2,499 men who have sex with men were randomized to receive once-daily dosing of placebo or 200-mg emtricitabine/ 300-mg tenofovir (Truvada). Eligible patients were initially HIV-negative but had evidence of high behavioral risk for HIV. Patients were followed every four weeks for up to 2.8 years (median follow-up period of 1.2 years). At every visit, patients received risk-reduction counseling, HIV testing, and diagnosis and treatment of symptomatic sexually transmitted infections. Exclusion criteria included elevations in hepatic enzyme levels and renal insufficiency.

Results: A total of 100 patients were diagnosed with new HIV infection during the study, with significantly fewer cases occurring in the drug treatment group than in the placebo group (36 versus 64, respectively; 44 percent relative risk reduction). The greatest benefit in preventing HIV transmission was noted in patients who previously had unprotected receptive anal intercourse (58 percent effective) compared with those who had not. Level of protection was not significantly different with regard to circumcision status, alcohol use, or age. There was no statistical difference between groups regarding elevation in serum creatinine levels. The treatment group reported more cases of nausea than the placebo group (22 versus 10 events, respectively; P = .04) and unintentional weight loss of 5 percent or more (34 versus 19 events, respectively; P = .04). Both groups were similar with respect to sexual practices and incidence of other sexually transmitted infections during the study. Self-reported high-risk behaviors decreased after study enrollment and remained lower than baseline throughout the study.

Conclusion: A once-daily oral combination of antiretroviral drugs helped protect against subsequent HIV infection in men who have sex with men. The authors caution that the optimal regimen for preexposure prophylaxis has not been established, and that the data in this study cannot necessarily be applied to other populations.