Brief Report: HIV-1 Evolution in Breakthrough Infections in a Human Trial of Oral Pre-exposure Prophylaxis With Emtricitabine and Tenofovir Disoproxil Fumarate

Daily PrEP with FTC/TDF is an effective HIV prevention strategy for persons at high risk of infection.1 In clinical trials, the level of HIV protection by PrEP was strongly correlated with antiretroviral (ARV) drug adherence.2 Across trials, infections in active arms were generally seen in participants with undetectable drug, although some seroconverters had measurable drug at the time of the first laboratory evidence of infection. Suboptimal PrEP adherence and HIV infection create an opportunity for continued drug activity during undiagnosed infection and raise questions on the impact of transient ARV drug pressure on early establishment of infection and acute virus dynamics. In some cohort studies of acute HIV infection, the degree of virus diversity during early infection was found to be predictive of the subsequent disease course3,4. The effect of PrEP on virus evolutionary dynamics and disease course will likely depend on the extent of ARV drug activity at the time of infection and before HIV diagnoses. The TDF2 was a phase III, randomized, double-blinded, placebo-controlled clinical trial of daily oral FTC/TDF among sexually active heterosexual men and women in Botswana.5 In this trial, the overall protective efficacy in the modified intention-to-treat analysis was 62.2%.5 In the as-treated analysis, in which follow-up data for participants were censored 30 days after their last reported study drug dose, the protective efficacy was 77.9%, with 4 HIV-1 infections in the FTC/TDF group and 19 in the placebo group. In this study, we used single genome amplification (SGA) and phylogenetic and sequence analysis to create a virological snapshot of HIV-1 in the 4 cases in the FTC/TDF arm of the TDF2 trial. We defined the number of transmitted/founder (T/F) viruses in these 4 infections and compared virus evolution dynamics during the first year of infection among the FTC/TDF arm cases and 5 seroconverters who were not taking study drug.