Drug Resistance During HIV Pre-Exposure Prophylaxis

Abstract

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.

Uptake and impact of facility‐based HIV self‐testing on PrEP delivery: a pilot study among young women in Kisumu, Kenya

“…The current World Health Organization guidelines do not recommend the use of HIVST by people taking PrEP [27] due to concerns about false-negative results. Taking PrEP with undetected HIV could lead to drug resistance, but a recent review of PrEP studies found that resistance selection for tenofovir disoproxil fumarate and emtricitabine with PrEP use is infrequent [28]. Evaluations of HIV rapid diagnostic tests (RDTs) among PrEP users have found variable sensitivities and specificities, with specificities >98% [29][30][31][32][33].…”

Barriers to the Wider Use of Pre-exposure Prophylaxis in the United States: A Narrative Review

“…Specific knowledge about PrEP medication, particularly how they work and the potential side effects, have also been highlighted as critical aspects for provision of PrEP by healthcare professionals [ 29 ]. Reluctance to prescribe PrEP may stem from provider misconceptions, such as concern that poor adherence may result in development of resistance [ 24 , 31 ] despite the fact that clinical evidence to date suggests that HIV drug resistance with PrEP use rarely occurs [ 32 , 33 ].…”

Piloting a partially self-financed mode of human immunodeficiency virus pre-exposure prophylaxis delivery for men who have sex with men in Hong Kong

“…Non-adherence to TDF/FTC could potentially lead to resistance if HIV infection occurs in the course of PrEP, though its incidence has remained low. 19 Condomless sex in conjunction with the omission of TDF/FTC, which can be referred as PrEP-unprotected condomless sex, was relatively uncommon. Risk compensation, defined as the increased practice of condomless sex in PrEP users, is an emerging concern.…”

“…20,21 Our results did not confirm any consistent increase of risk compensation behaviours, an observation shared by other recent studies. 4,22,23 Increased incidence of STI could be more prevalent in the initial period of PrEP introduction 19,24 or restricted to a subpopulation of MSM regardless of PrEP use. 20 It is uncommon to see MSM starting to engage in condomless anal sex after PrEP initiation.…”