BCL-2 Inhibition via Venetoclax at ART Initiation Induces Long-Term Reduction of the Intact SIV Reservoir.

ABSTRACT: The anti-apoptotic molecule BCL-2 favors the maintenance of the CD4⁺ T-cell reservoir during Human Immunodeficiency Virus (HIV) infection. We investigated directly in-vivo whether BCL-2 inhibition using venetoclax at the initiation of antiretroviral therapy (ART) would reduce the size of the viral reservoir. Twenty-four SIV_mac239-infected rhesus macaques (RMs) initiated ART at day 14 post-infection (p.i.), alone or with a 10-day treatment with venetoclax or venetoclax plus CD8α depletion, and followed up to day 294 p.i. A rapid, statistically significant, and sustained reduction in the intact SIV reservoir was observed in venetoclax-treated RMs in blood and lymph nodes (LNs). This reduction was driven by reduced survival and depletion of CD4⁺T-cell subsets

SUBMITTER: Salinas TRW 

PROVIDER: S-EPMC12288516 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature