Using mathematical modelling to better understand HIV/SIV infection

Date: Thursday 6 April 2023

Abstract

The development of combination antiretroviral therapy (ART) has revolutionized the treatment of HIV. ART treatment reduces viral levels below detection among people living with HIV, but ART treatment is not a cure. Following cessation of ART treatment, HIV virus generally rebounds within a matter of weeks. Therefore, lifelong adherence to ART treatment is required. Despite the advances in HIV treatment, there are still a number of unanswered basic science questions; the answers to which may aid in the development of effective cures.

In this talk, I will discuss how mathematical analysis of experimental data increases our understanding of 1) the processes at play during establishment of infection and 2) the viral replication cycle. The majority of sexually transmitted HIV infections are initiated by a single viral particle, and this has given rise to the hypothesis of an anatomical barrier at the site of infection, which inhibits the majority of infectious particles from establishing systemic infection. In non-human primate experiments, large inoculation doses leading to multiple founding viruses can be administered either prior to (e.g., intravaginal inoculation) or after (e.g., intravenous inoculation) such a theoretical anatomical barrier. We use bootstrapping analysis of early infection data from such experiments to assess the evidence supports the existence of such an anatomical barrier. In the second part of my talk, I will discuss viral production by individual cells. It is often assumed that all infected cells produce virus at the same rate, however our data indicates large heterogeneity between cells. I will present our characterization of this heterogeneity and the implications for our understanding of the progression of viral infection within an individual.