Background:  We conducted a randomized, 3-arm trial of oral antiretroviral pre-exposure prophylaxis (PrEP) among heterosexual couples from Kenya and Uganda in which one member was HIV-1 seronegative and the other HIV-1 seropositive (the Partners PrEP Study). On July 10, 2011 the independent Data and Safety Monitoring Board, reviewing data through May 31, recommended that the results of the study be publicly reported and the placebo arm discontinued, because of clear demonstration of HIV-1 protection from PrEP. We report final results from the primary study analysis, including updated data through July 10, 2011.

Methods:  Seronegative partners were randomly assigned to once-daily tenofovir (TDF), combination emtricitabine/tenofovir (FTC/TDF), or matching placebo and followed monthly for as long as 36 months. At enrollment, HIV-1-infected partners were not eligible for ART under national guidelines. All couples received standard HIV-1 treatment and prevention services, including individual and couples risk-reduction counseling and condoms.

Results:  We enrolled 4758 couples; for 62%, the HIV-1-uninfected partner was male. Adherence to study medication was 97%, measured by monthly pill count of unused study product, and retention was ≥96%. Of 82 post-randomization HIV-1 infections, 17 were among those assigned TDF, 13 among those assigned FTC/TDF, and 52 among those assigned placebo; HIV-1 risk was reduced by 67% by TDF (95%CI 44 to 81, p <0.0001) and 75% by FTC/TDF (95%CI 55 to 87, p <0.0001). HIV-1 protective effects of FTC/TDF and TDF were not significantly different (p = 0.23), and both study medications significantly reduced HIV-1 risk in both men and women. The rate of serious medical events was similar across the study arms. PrEP was associated with modest increased gastrointestinal symptoms, primarily in the first month. HIV-1 resistance was rare:  among 8 subjects infected at randomization, 1 developed the K65R mutation and 1 the M184V mutation; no subjects who acquired HIV-1 after randomization developed K65R or M184V mutations.

Conclusions:  Among heterosexual men and women with a known HIV-1-infected partner, once-daily oral TDF and FTC/TDF safely and substantially reduced the risk of HIV-1 infection, when provided in the context of other HIV-1 prevention services. Demonstration projects are needed to evaluate targeted PrEP delivery models for highest-risk populations, including HIV-1 serodiscordant couples.