The effect of combining HIV latency reversal with inhibition of phosphoinositide-3 kinases or B-cell lymphoma-2 on the HIV reservoir

Abstract

The persistence of latently infected CD4 + T-cells in people with HIV (PWH) on suppressive antiretroviral therapy (ART) is the major barrier to an HIV cure. We investigated the impact of two classes of pro-apoptotic drugs, phosphoinositide-3 kinases (PI3K) inhibitors or the B cell lymphoma 2 (Bcl-2) inhibitor venetoclax on depletion of latently infected CD4 + T-cells when administered ex vivo either alone or in combination with a latency reversing agents (LRA) to induce expression of pro-apoptotic viral proteins. We quantified cell death in three latently infected cell lines (J-Lat clones) and the parental cell line (Jurkat) using a live dead stain and flow cytometry. Using CD4 + T-cells iso..