Extensive characterization of HIV-1 reservoirs reveals links to plasma viremia before and during analytical treatment interruption

• Published in: Cell reports (Cambridge) Vol. 39; no. 4; p. 110739
• Main Authors: Cole, Basiel, Lambrechts, Laurens, Boyer, Zoe, Noppe, Ytse, De Scheerder, Marie-Angélique, Eden, John-Sebastian, Vrancken, Bram, Schlub, Timothy E., McLaughlin, Sherry, Frenkel, Lisa M., Palmer, Sarah, Vandekerckhove, Linos
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.04.2022
• Subjects: analytical treatment interruption; Anti-Retroviral Agents - therapeutic use; antiretroviral therapy; CD4-Positive T-Lymphocytes; cellular proliferation; clonal expansion; full-length HIV sequencing; HIV; HIV Infections; HIV Seropositivity - drug therapy; HIV-1; Humans; integration site sequencing; latency; Proviruses - genetics; rebound; replication competency; Viremia - drug therapy; Virus Latency; full-length HIV sequencing; rebound; HIV; integration site sequencing; analytical treatment interruption; antiretroviral therapy; latency; CP: Microbiology; clonal expansion; replication competency; cellular proliferation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110739

The HIV-1 reservoir is composed of cells harboring latent proviruses that have the potential to contribute to viremia upon antiretroviral treatment (ART) interruption. While this reservoir is known to be maintained by clonal expansion of infected cells, the contribution of these cell clones to residual viremia and viral rebound remains underexplored. Here, we conducted an extensive analysis on four ART-treated individuals who underwent an analytical treatment interruption (ATI), characterizing the proviral genomes and associated integration sites of large infected clones and phylogenetically linking these to plasma viremia. We show discrepancies between different assays in their ability to assess clonal expansion. Furthermore, we demonstrate that proviruses could phylogenetically be linked to plasma virus obtained before or during an ATI. This study highlights a role for HIV-infected cell clones in the maintenance of the replication-competent reservoir and suggests that infected cell clones can directly contribute to rebound viremia upon ATI. [Display omitted] •Assays to study clonal expansion of HIV-1-infected cells introduce distinct biases•Sequence matches are detected between low-level/residual viremia and proviruses•Infected cells that contribute to rebound are often maintained by clonal expansion Cole, Lambrechts, et al. study the proviral HIV-1 landscape in four participants undergoing an antiretroviral treatment interruption. Matches between plasma viruses recovered during and before the interruption and proviruses found in cell clones highlight a role for clonal expansion in the maintenance of the clinically relevant viral reservoir.