The immunophenotype and proviral landscape of HIV-infected CD4 T cells during antiretroviral therapy

Abstract

Significance The persistence of HIV in CD4+ T cells during antiretroviral therapy (ART) remains a barrier to cure. To study this reservoir, we developed an open-source DAb-seq platform that sequences proviral DNA and surface epitopes in single cells and profiled ~527,000 CD4 T cells from individuals on ART. HIV-infected cells were enriched in memory T cell subsets, and surface protein differences between HIV+ and HIV− cells mirrored this distribution. Although memory T cells contained most infected cells, proviruses with more genomic regions detected were disproportionately enriched in Naïve, Transitional memory, and Regulatory subsets, suggesting that subset-specific processes govern proviral fate. This work presents a high-resolution immunophenotypic map of the HIV reservoir, highlighting the diversity of infected cells.