Factors Influencing the Emergence and Spread of HIV Drug Resistance Arising from Rollout of Antiretroviral Pre-Exposure Prophylaxis (PrEP)

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.

How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts' Opinion and Its Influence on the Projected Public Health Impact

“…The use of ARV as PrEP by infected individuals leads to emergence of drug resistance (acquired drug resistance, ADR) because PrEP is not designed for treatment and is unlikely to exert complete HIV suppression [24,26,30,34,35,56]. The rate of resistance emergence may depend on the consistency of PrEP use (adherence) since it controls the ARV drug concentrations and from there the pressure on the HIV virus.…”

“…Reversion of resistance HIV containing resistance associated mutations against PrEP can revert to wild-type when PrEP is discontinued or when an ARV-naïve host is infected with resistant HIV [24,26,34,35]. The rate of reversion may be substantially slower in ARV-naïve individuals with TDR compared to former PrEP users who developed ADR on PrEP [57][58][59].…”

“…Reduced fitness of the drug-resistant HIV Resistance carriers may be less infectious than those infected with wild-type HIV as a result of the reduced replication capacity [24,26,30,34,35,56] of the resistant HIV, which in turn can reduce the viral load. It may result in lower viral concentration that affects the likelihood of transmission.…”

“…• PrEP efficacy against drug-resistant HIV PrEP may provide reduced protection against PrEP-generated resistance since those HIV strains have managed to escape the ARV pressure of PrEP in infected users [24,26,34,35]. Reduced effectiveness of PrEP has been suggested by studies in macaques challenged with resistant SIV.…”

Les moyens de prévention de l’infection à VIH à base d’antirétroviraux

“…Des stratégies ciblant les travailleuses du sexe et leurs clients ou les femmes de 15 à 35 ans avec des taux de couverture modérés à élevés [42] pourraient réduire l'incidence de 5 à 20 % dans la population générale, si la PrEP s'avérait efficace à 90 % [42,43]. Des stratégies proposant la PrEP en population générale pourraient réduire le nombre de nouvelles infections au cours des dix prochaines années de 20 à 30 % si la couverture était de 60 % et l'efficacité de 75 % [43,44]. L'impact de la PrEP pourrait diminuer ou s'avérer négatif si son introduction était accompagnée d'une augmentation des comportements à risque [45], surtout dans les populations où l'utilisation du préservatif est très élevée [42].…”