Human immunodeficiency virus 1 Targeted Locus (Loci)

Background Pre-exposure prophylaxis (PrEP) with emtricitabine plus tenofovir disproxil fumarate (FTC/TDF) or TDF alone reduces HIV acquisition. Understanding the risk of antiretroviral resistance selected by PrEP during breakthrough infections is important because of the risk of treatment failure during subsequent antiretroviral use. Methods Within the largest randomized trial of FTC/TDF versus TDF as PrEP, plasma samples were tested for resistance mutations associated with FTC (K65R, M184IV) and TDF (K65R, K70E) using 454 sequencing. Results Of 121 HIV seroconverters, 25 had received FTC/TDF, 38 TDF, and 58 placebo. Plasma drug levels in 26 individuals indicated PrEP use during or after HIV acquisition, of which 5 had resistance mutations associated with their PrEP regimen. Among those with PrEP drug detected during infection, resistance was more frequent in the FTC/TDF arm (4/7, 57%) compared to the TDF arm (1/19, 5.3%; p=0.01) due to the FTC-associated mutation M184IV. Of these cases, 3 had unrecognized acute infection at PrEP randomization, and 2 were HIV negative at enrollment. Conclusions These results suggest that resistance selected by PrEP is rare, but can occur both with PrEP initiation during acute seronegative HIV infection and in PrEP breakthrough infections, and that more resistance is selected by FTC than TDF.