Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 study

Background: The Preexposure Prophylaxis Initiative (iPrEX) study found that pre-exposure prophylaxis using antiretroviral medications (PrEP) significantly reduced HIV transmission amongmen who have sex with men. However, the FemPrEP study among high risk women showed no such protective effect. Therefore, additional safety and efficacy data among heterosexual men and women are needed.
Methods: We randomly assigned HIV-seronegative participants 18-39 years of age to receive either oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) or matching placebo once daily. Participants attended monthly visits for HIV testing and risk reduction counseling, sexually-transmitted infection management, and adverse event monitoring.
Results: Of 2532 volunteers screened, 1219 were randomized; 45.7% female. Participants were followed for 1549 person-years (median 1.1 years; maximum 3.7 years). Adherence by pill count was similar in both arms (TDF-FTC 84.1% vs. placebo 83.7%, p=0.79). Comparable proportions of participants in both arms reported >1 sexual partner in the prior month and percentage of vaginal episodes with condom use (TDF-FTC 14.2% vs. placebo 14.1%, p=0.86; TDF-FTC 81.9% vs. placebo 79.7%, p=0.21, respectively). Nausea/vomiting and dizziness occurred more commonly among TDF-FTC participants compared to placebo (28.8% vs. 11.9%, p< 0.0001; 15.3% vs. 10.5%, p=0.0143, respectively). There was no difference in serious adverse events between groups (TDF-FTC 9.2% vs. placebo 8.5%, p=0.58). Using modified intent-to-treat analysis including the 33 participants who became HIV-infected during study participation (63.6% female), 9 received TDF-FTC and 24 received placebo correlating to an overall protective efficacy of 62.6% (95% confidence intervals, CI, 21.5, 83.4; p=0.0133). Limiting analysis to participants on study medication when infected, the protective efficacy was 77.9% (95% CI 41.2, 93.6; p=0.0053).
Conclusion: Daily TDF-FTC was effective and safe for prevention of HIV infection among heterosexual men and women compared to placebo. Data from two ongoing studies and TDF-FTC drug level testing in TDF2 participants will further define the role of PrEP among heterosexual populations.

M.C. Thigpen1, P.M. Kebaabetswe2, D.K. Smith1, T.M. Segolodi2, F.A. Soud1, K. Chillag1, L.I. Chirwa2, M. Kasonde2, R. Mutanhaurwa2, F.L. Henderson1, S. Pathak1, R. Gvetadze1, C.E. Rose1, L.A. Paxton1, for the TDF2 Study Group
1Center for Disease Control and Prevention (CDC), Division of HIV/AIDS Prevention, Atlanta, United States, 2BOTUSA, HIV Prevention Research Unit, Gaborone, Botswana