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

B Cole, L Lambrechts, Z Boyer, Y Noppe… - Cell reports, 2022 - cell.com
B Cole, L Lambrechts, Z Boyer, Y Noppe, MA De Scheerder, JS Eden, B Vrancken
Cell reports, 2022cell.com
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 …
Summary
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.
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