Venetoclax delays viral rebound in a humanized mouse model of HIV infection
Venetoclax depletes intact HIV DNA ex vivo in cells from people living with HIV on ART
The HIV reservoir is enriched in cells with higher expression of BH3-only proteins
Persistence of HIV-1 on ART necessitates lifelong treatment and represents the key obstacle to cure. Despite early optimism, it is apparent that transcriptional reactivation of latently infected cells is not sufficient to induce cell death and delay viral rebound,
and recent evidence suggests that antiapoptotic mechanisms are in place that maintain survival of latently infected cells despite the highly apoptotic environment of productive infection.
Venetoclax is a BH3 mimetic that specifically antagonizes Bcl-2 and is approved for the treatment of chemotherapy-refractory chronic lymphocytic leukemia (CLL).
While the ability of venetoclax to kill latent and productively infected cells in vitro has been explored by others, we sought to examine the efficacy of venetoclax in a physiologically relevant in vivo model of HIV-1 persistence on ART and in CD4+ T cells from people living with HIV (PLWH) on ART.