HIV-1 uninfected individuals within HIV-1 discordant partnerships are at high-risk for HIV-acquisition. The majority of HIV-1 transmissions to adults in Africa occur within stable, HIV-1 discordant couples. Novel strategies to prevent HIV-1 transmission within discordant couples, especially interventions that might allow pregnancy to occur safely, are urgently needed. Pre-exposure chemoprophylaxis, in which an HIV-1 uninfected individual at high risk for contracting HIV-1 takes antiretroviral medications to maintain blood and genital drug levels sufficient to prevent HIV-1 acquisition, has been proposed as a potential HIV-1 prevention strategy. A randomized, blinded, placebo-controlled trial is required to demonstrate if PrEP decreases HIV-1 acquisition and has an acceptable safety profile when given to HIV-1 uninfected individuals within HIV-1 discordant partnerships.

Both tenofovir disoproxil fumarate (TDF) and co-formulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) have been proposed as possible safe and effective medications to serve as pre-exposure chemoprophylaxis. The potential for differential safety, cost, and efficacy for these two medications justifies evaluating both, against placebo, in a single clinical trial. This trial will directly answer whether PrEP decreases HIV-1 acquisition among HIV-1 uninfected individuals within HIV-1 discordant couples, a very high-risk heterosexual population who could benefit from this type of intervention, if found to be safe and efficacious.