The HIV-1 latent reservoir is largely sensitive to circulating T cells
Joanna Warren, Shuntai Zhou, Yinyan Xu, Matthew Moeser, Daniel MacMillan, Jennifer Kirchherr, Julia Marsh Sung, Nadia R. Roan, Adaora A. Adimora, Sarah Joseph, JoAnn Kuruc, Cynthia L. Gay, David M. Margolis, Nancie M. Archin, Zabrina L. Brumme, Ronald Swanstrom, Nilu Goonetilleke
Abstract
HIV-1-specific CD8+ T cells are an important component of HIV-1 curative strategies. Viral variants in the HIV-1 reservoir may limit the capacity of T cells to detect and clear virus-infected cells. We investigated the patterns of T cell escape variants in the replication-competent reservoir of 25 persons living with HIV-1 (PLWH) durably suppressed on antiretroviral therapy (ART). We identified all reactive T cell epitopes in the HIV-1 proteome for each participant and sequenced HIV-1 outgrowth viruses from resting CD4+ T cells. All non-synonymous mutations in reactive T cell epitopes were tested for their effect on the size of the T cell response, with a≥50% loss defined as an escape mutation. The majority (68%) of T cell epitopes harbored no detectable escape mutations. These findings suggest that circulating T cells in PLWH on ART could contribute to control of rebound and could be targeted for boosting in curative strategies.