Single-Agent TDF Versus Combination FTC/TDF PrEP Among Heterosexual Men and Women

Background: Antiretroviral pre-exposure prophylaxis (PrEP), using daily oral tenofovir (TDF) alone or combination emtricitabine/tenofovir (FTC/TDF), has been demonstrated to be an efficacious HIV-1 prevention intervention in four clinical trials. Whether single-agent TDF PrEP has comparable efficacy to dual-agent FTC/TDF PrEP is unknown. Methodology: The Partners PrEP Study was a randomized, double-blind, placebo-controlled three-arm trial of daily oral TDF and FTC/TDF PrEP among heterosexual HIV-1 uninfected members of HIV-1 serodiscordant couples from Kenya and Uganda. In July 2011, the trial’s placebo arm was discontinued because of clear demonstration of HIV-1 protection from PrEP; compared to placebo, HIV-1 prevention efficacy was 67% for TDF and 75% for FTC/TDF, and TDF and FTC/TDF efficacy were not significantly different (p=0.23). After July 2011, to gather additional comparative information about single-versus dual-agent PrEP, the trial’s active arms were continued in a blinded fashion and the participants initially randomized to placebo were offered re-randomization to TDF or FTC/TDF PrEP. Data collection was completed in December 2012. Results: 4747 HIV-1 serodiscordant couples were enrolled and followed; for 62%, the HIV-1 uninfected partner was male. A total of 52 post-randomization HIV-1 infections occurred among individuals assigned to the active PrEP arms: 30 prior to and 22 after July 2011. Of these 52 infections, 31 were among those assigned TDF (incidence 0.7 per 100 person-years) and 21 were among those assigned FTC/TDF (incidence 0.5 per 100 person-years); for comparison, HIV-1 incidence in the placebo arm prior to July 2011 was 2.0 per 100 person-years. HIV-1 prevention efficacy for FTC/TDF compared to TDF alone was not statistically significantly different: HR 0.67, 95% 0.39-1.17, p=0.16. Detection of tenofovir in plasma samples, measured in seroconverters and a subset of non-seroconverters, was associated with an 85% relative risk reduction in HIV-1 acquisition for the TDF arm and 93% for the FTC/TDF arm (both p<0.001). By consensus sequencing, no cases of HIV-1 antiretroviral resistance related to TDF or FTC were identified in HIV-1 seroconverters after July 2011. Conclusions: Among heterosexual men and women, once-daily oral TDF and FTC/TDF are safe and provide high and comparable risk reduction against HIV-1 acquisition.