Modeling HIV viral dynamics and ART

Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads to levels undetectable using commercial testing. Typically, suspension of therapy is followed within weeks by rebound of viral loads to high, pre-therapy level. However recent observations give nuance to that statement: in a small fraction of cases, rebound may be delayed by months, years, or even possibly, permanently, termed post-treatment control (PTC). We begin with a discussion of viral dynamics in the presence of ART and circumstances that permit viral rebound. We follow that with a discussion of mechanisms that may permit PTC, hypothesizing that early treatment induces PTC by restricting the latent reservoir size. Activation of cells latently infected with HIV are thought to drive viral rebound, and early treatment may render it sufficiently small for immune responses to control infection after treatment cessation. ODE model analysis reveals a range in immune response-strengths where a patient may show bistability between viral rebound or PTC. Finally, in case of viral rebound, data reveals significant heterogeneity in timing and ensuing dynamics. We will discuss stochastic modeling to investigate that heterogeneity, relying on data from Li et al. (2016). We will finish with an outlook on developing science in this area and some preliminary modeling on biomarkers for prediction of control or time to rebound.

Jessica Conway  was a UBC postdoc with Daniel Coombs from 2008-2012. She is now an associate professor of mathematics and biology graduate faculty at Penn State Eberly College of Science.