HIV DAb-Seq of ART-Treated Individuals

Despite effective antiretroviral therapy (ART), HIV remains an incurable disease. The latent HIV reservoir is a central obstacle to a cure. It consists of rare CD4+ cells harboring replication-competent proviral DNA that inevitably resumes viremia upon ART interruption. Despite their importance, little is known about the properties of these latently infected CD4+ T-cells. In this study, we investigate the immunophenotype of HIV-infected CD4+ T-cells from people living with HIV (PLWH) who have been successfully treated with ART for at least two years. By leveraging and improving our high-throughput single-cell technology, DAb-seq, we detect infected CD4+ T-cells in peripheral blood mononuclear cells (PBMCs) of PLWH using a panel of 10 HIV DNA-targeting amplicons, while simultaneously measuring the immunophenotype of the host cells using a panel of 153 DNA-encoded antibodies. We observe a biased ratio of cell infection across distinct CD4+ T-cell subsets, but after accounting for this difference, no HIV-specific phenotypic signature emerges. Our findings suggest that key differences exist in the fate of cells with intact proviruses between compartments, emphasizing the importance of sensitive single-cell DNA technologies that simultaneously measure provirus intactness and host cell phenotypes.]]>
Samples from people living with HIV were sourced from the HIV Reservoir Assay Validation and Evaluation Network (RAVEN cohort). Samples were collected from ART-suppressed people living with HIV under IRB-approved protocols. To study the latent reservoir we selected samples from people who have been on effective long term ART (3 years or more) and which exhibit a high frequency of infected CD4+ T-cells.]]>