GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301433/primaryOK200TranscriptomicsMacaca mulattaExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301433GEOGSEfalseBCL-2 Inhibition at antiretroviral therapy initiation reduces the intact SIV reservoir in macaquesThe 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 SIVmac239-infected rhesus macaques (RMs) were initiated on ART at day 14 post-infection (p.i.), alone or in combination with either 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 that critically contribute to the reservoir. CD4+ T-cells that persisted after venetoclax treatment exhibited elevated per-cell levels of BCL-2, reduced expression of pro-apoptotic molecules such as PUMA, increased expression of additional anti-apoptotic molecules, including BCL-xL, and a partial reduction in apoptotic sensitivity in ex vivo assays. These findings provide mechanistic insights for the venetoclax-induced pro-cell death changes in CD4+ T-cells, support the rationale for extended venetoclax dosing, and suggest that combining BCL-2 inhibition with agents targeting additional anti-apoptotic molecules can enhance clearance of the viral reservoir in HIV cure strategies.2026/06/28GSE301433GSM9083235GSM9083224GSM9083234GSM9083223GSM9083237GSM9083226GSM9083215GSM9083236GSM9083225GSM9083217GSM9083228GSM9083227GSM9083216GSM9083219GSM9083229GSM9083218GSM9083220GSM9083231GSM9083230GSM9083233GSM9083222GSM9083232GSM908322127943301433Macaca mulatta