What do mathematical models tell us about the emergence and spread of drug-resistant HIV?

Abstract

To discuss recent HIV epidemic models examining the transmission of antiretroviral (ARV) drug resistance. A relatively small number of recent transmission models have investigated ARV resistance in the context of therapeutic, combined ART (cART); ARV-vaginal microbicides (ARV-VMB); and oral pre-exposure prophylaxis (PrEP). Models of cART use have highlighted potential concerns about future resistance transmission, particularly in resource-constrained settings, and have emphasized the benefits of viral load monitoring in limiting resistance spread. PrEP models have concluded that inadvertent use by HIV-infected individuals could increase resistance prevalence, and that risk compensation by PrEP users could limit their beneficial effects on HIV transmission. ARV-VMB models have demonstrated that whereas resistance can reduce prophylactic effectiveness in preventing HIV acquisition of female ARV-VMB users, it may concomitantly benefit users' male partners if the resistant strains that female users acquire are less transmissible than wild-type strains. The models have examined the balance between these two factors at the population level. Recent HIV transmission models have adopted a wide assortment of structures and assumptions to explore drug resistance in the context of different ARV interventions in various settings. There is a need for future work emphasizing the simultaneous effects of multiple ARV interventions, as well as the public health impact of resistance, not just its prevalence.