Abstract

BackgroundThe potential for emergence and spread of HIV drug resistance from rollout of antiretroviral (ARV) pre-exposure prophylaxis (PrEP) is an important public health concern. We investigated determinants of HIV drug resistance prevalence after PrEP implementation through mathematical modeling.MethodologyA model incorporating heterogeneity in age, gender, sexual activity, HIV infection status, stage of disease, PrEP coverage/discontinuation, and HIV drug susceptibility, was designed to simulate the impact of PrEP on HIV prevention and drug resistance in a sub-Saharan epidemic.Principal FindingsAnalyses suggest that the prevalence of HIV drug resistance is influenced most by the extent and duration of inadvertent PrEP use in individuals already infected with HIV. Other key factors affecting drug resistance prevalence include the persistence time of transmitted resistance and the duration of inadvertent PrEP use in individuals who become infected on PrEP. From uncertainty analysis, the median overall prevalence of drug resistance at 10 years was predicted to be 9.2% (interquartile range 6.9%–12.2%). An optimistic scenario of 75% PrEP efficacy, 60% coverage of the susceptible population, and 5% inadvertent PrEP use predicts a rise in HIV drug resistance prevalence to only 2.5% after 10 years. By contrast, in a pessimistic scenario of 25% PrEP efficacy, 15% population coverage, and 25% inadvertent PrEP use, resistance prevalence increased to over 40%.ConclusionsInadvertent PrEP use in previously-infected individuals is the major determinant of HIV drug resistance prevalence arising from PrEP. Both the rate and duration of inadvertent PrEP use are key factors. PrEP rollout programs should include routine monitoring of HIV infection status to limit the spread of drug resistance.

Highlights

  • Antiretroviral (ARV) pre-exposure prophylaxis (PrEP) is a promising HIV prevention strategy [1,2]

  • Inadvertent preexposure prophylaxis (PrEP) use in previously-infected individuals is the major determinant of HIV drug resistance prevalence arising from PrEP

  • PrEP rollout programs should include routine monitoring of HIV infection status to limit the spread of drug resistance

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Summary

Introduction

Antiretroviral (ARV) pre-exposure prophylaxis (PrEP) is a promising HIV prevention strategy [1,2]. There is widespread concern, about the potential emergence and spread of HIV drug resistance arising from PrEP rollout, in resource-constrained settings, where antiretroviral treatment options are limited. This concern is amplified by the possibility that the same antiretroviral drugs will be used for both treatment and PrEP. The focus of the current work was to identify major determinants of HIV drug resistance prevalence after PrEP implementation rather than prediction of actual outcomes. The potential for emergence and spread of HIV drug resistance from rollout of antiretroviral (ARV) preexposure prophylaxis (PrEP) is an important public health concern. We investigated determinants of HIV drug resistance prevalence after PrEP implementation through mathematical modeling

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