HIV-1 latency reversal agent boosting is not limited by opioid use

• DOI: 10.1172/jci.insight.185480
• Publication Date: 2024-10-29T16:00:32Z
• Authors: Tyler Lilie; Jennifer Bouzy; Archana Asundi; Jessica Taylor; Samantha Roche; Alex Olson; Kendyll Coxen; Heather Corry; Hannah Jordan; Kiera Clayton; Nina Lin; Athe Tsibris
• Keywords: Boosting

Opioid use may impact the HIV-1 reservoir and its reversal from latency. We studied forty-seven virally suppressed people with HIV (PWH) observed that lower concentration of latency agents (LRA), used in combination small molecules did not reverse latency, synergistically increased magnitude re-activation ex vivo, regardless opioid use. This LRA boosting, which combined a Smac mimetic or low-dose protein kinase C agonist histone deacetylase inhibitors, generated significantly more unspliced transcription than phorbol 12-myristate 13-acetate (PMA) ionomycin (PMAi), maximal known reactivator. boosting associated greater acetylation, modulated surface activation-induced markers, altered T cell production TNFα, IL-2, IFNγ. reservoirs PWH contained polyadenylated (polyA) virus mRNA, ratios were resting total CD4+ cells correct to 1:1 PMAi exposure. characterized treated infection as period inefficient, absent, transcription. Multiply spliced transcripts virion consistently increase suggesting presence persistent post-transcriptional block. can be leveraged probe mechanisms an effective cellular program.