Clinical studies have demonstrated that use of tenofovir disoproxil fumarate with or without emtricitabine as antiretroviral preexposure prophylaxis (PrEP) can decrease the risk of HIV acquisition when medication adherence is high. However, the potential for PrEP to promote antiretroviral resistance remains an important public health consideration. We performed a search of the medical literature to identify studies that address HIV drug resistance during PrEP use. In this review, we summarize findings about emergent drug resistance during clinical trials of PrEP, case reports of seroconversions in adherent PrEP patients, and animal studies of PrEP effectiveness against drug resistant viral strains. We also discuss the potential utility of novel PrEP formulations for protection against drug resistant HIV, the impact of drug resistance on HIV treatment options, and mathematical models that estimate the potential contribution of PrEP to population-level drug resistance. Evidence suggests that selection for HIV drug resistance with PrEP use is infrequent and most likely to occur when PrEP is used during undiagnosed acute HIV infection. Breakthrough infections during PrEP use with high adherence are possible, but appear to be rare. The prevalence of drug resistant HIV strains needs to be monitored as PrEP is scaled-up. However, the benefit of decreased HIV incidence with wider PrEP use is likely to outweigh the risk of harms from possible increases in the prevalence of HIV drug resistance.

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