Speaker
Description
Though viral load is suppressed, a latent reservoir of HIV persists during antiretroviral therapy (ART), meaning people living with HIV (PWH) must take ART indefinitely. We have hypothesized that persistence is driven predominantly by natural processes of CD4+ T cells harboring integrated HIV DNA proviruses. Here we measure and compare the clonality and clonal dynamics of HIV proviruses to those of resting memory CD4 TCRβ repertoires from the same PWH. We develop a mathematical model of a comprehensive data set including total levels and clonal dynamics. The model tracks stochastic proliferative dynamics of CD4+ T cells, some of which carry HIV proviruses. We test models with differing mechanisms and demonstrate that HIV-specific negative selection -- additional death rates for cells harboring intact proviruses -- is required to recapitulate all experimental observations. These results project long-term reservoirs that are predominantly defective and highly quiescent, informing curative therapeutics attempting to reduce HIV reservoirs.
