Speaker
Description
Antiretroviral therapy (ART) for HIV-1 infection is not curative. Treatment interruption typically results in viral rebound and progressive disease, necessitating lifelong ART. However, a small fraction of people living with HIV achieve long-term post-treatment control (PTC) of the virus, offering hope that strategies may be devised that obviate the need for lifelong treatment. While mechanisms underlying PTC remain to be understood, recent studies have identified early treatment initiation as a key factor and suggested a role for CD8 T cells. Here, we developed a within-host mathematical model to elucidate the associated mechanisms. We hypothesized, based on immunological studies, that upon infection, virus-specific CD8 T cells accumulate ‘antigenic experience’ through continual exposure to the antigen, which compromises their survival. Early ART initiation limits this experience, preserving memory CD8 T cells and enabling better response to rebounding virus post-ART. We fit the model to longitudinal data from a recent macaque study using a nonlinear mixed effects approach. The model exhibited bistability. One stable steady state had low viral load and high memory cell levels, and the other vice versa, recapitulating PTC and progressive disease, respectively. Early treatment initiation made the control state more accessible. The model predicted treatment initiation times and the associated memory CD8 T cell pool sizes for maximizing PTC, informing interventions.
