TY - JOUR T1 - Evolution of HIV virulence in response to widespread scale up of antiretroviral therapy: a modeling study JF - bioRxiv DO - 10.1101/039560 SP - 039560 AU - Joshua T. Herbeck AU - John E. Mittler AU - Geoffrey S. Gottlieb AU - Steven Goodreau AU - James T. Murphy AU - Anne Cori AU - Michael Pickles AU - Christophe Fraser Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/02/21/039560.abstract N2 - 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. UNAIDS has set forth an ambitious 90-90-90 strategy for 2020. 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 usage 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 also repeated our analysis using a separate model calibration, as a sensitivity analysis, and found that predicted impact of ART on virulence was relatively insensitive to calibration. We explored two distinct ART scenarios, at increasing coverage levels: ART initiation based on patients reaching a CD4+ T cell count threshold, or based on time elapsed since infection (a scenario that mimics the “universal testing and treatment” aspirations in the 90-90-90 UNAIDS targets. We found that HIV virulence is generally unchanged in scenarios of CD4-based initiation. However, with ART initiation based on time since infection (universal test and treat), virulence can increase moderately within several years of ART rollout, under high coverage levels and early treatment initiation albeit within the context of epidemics that are rapidly decreasing in size. We also show that, compared to non-evolutionary HIV epidemic models, allowing for evolving virulence predicts greater declines in HIV incidence after ART rollout. 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. ER -