Speaker
Description
In this study, we studied an HIV-1 infected individual who experienced a 48 month delay between acute infection and seroconversion, and despite undergoing ART, had a viral load more typical of untreated individuals. To investigate the evolution of HIV-1 in this unique individual, we whole-genome, deep-sequenced HIV-1 plasma RNA from four samples taken over 1737 days. We compared evolutionary metrics observed in this individual to those from a published study of WG NGS data from ten untreated HIV-1 seroconverters with similar viral loads. This comparison revealed only a minimal increase in divergence in our study individual, despite the measurable viremia over the first 414 days of study. To explore mechanistic explanations for this finding, we developed a within-host modelling framework of HIV-1 infection that simultaneously tracks viral and evolutionary dynamics. We show how a model in which antibodies contribute to the decay rate of a population of relatively long-lived infected cells is consistent with our observation of a lack of nonsynonymous divergence despite measurable viremia. Our work highlights how the application of viral and evolutionary modelling to the study of seronegative individuals offers an untapped avenue for investigating the role of antibodies in HIV-1 infection.
