Evolution of HIV virulence in response to widespread scale up of antiretroviral therapy: a modeling study

Abstract

There are global increases in the use of HIV antiretroviral therapy (ART), guided by clinical benefits of early ART initiation, and the efficacy of treatment as prevention of transmission. Separately, it has been shown theoretically and empirically that HIV virulence can evolve over time. Observed virulence levels may reflect an adaptive balance between infected lifespan and per-contact transmission rate. Critically, the potential effects of widespread ART on HIV virulence are unknown. To predict these effects, we used an agent-based stochastic model to simulate changes in HIV virulence, using set point viral load as a virulence proxy. We calibrated our epidemic model to the prevalence and incidence trends of South Africa. We repeated our analysis using a separate calibration, as a sensitivity analysis, and found that predicted impact of ART on virulence was relatively insensitive to calibration. We explored two ART scenarios, at increasing coverage : ART initiation based on patients reaching a CD4 cell count threshold, or based on time elapsed since infection (a scenario that mimics the \"universal testing and treatment\" aspirations). We found that HIV virulence is generally unchanged in scenarios of CD4-based initiation. However, with ART initiation based on time since infection, virulence can increase moderately within several years of ART rollout, under high coverage and early treatment initiation, albeit within the context of rapidly shrinking epidemics. Our modeling study suggests that increasing virulence driven by universal test and treat is likely not a major public health concern, but could be monitored in sentinel surveillance, in a manner similar to transmitted drug resistance.