Bivalent SMAC mimetic APG-1387 reduces HIV reservoirs and limits viral rebound in humanized mice.

ABSTRACT: Latent viral reservoirs (VRs) represent a main barrier to HIV cure. Thus, developing new approaches that can purge and eliminate VRs paves the path toward achieving an HIV-1 cure. APG-1387, a bivalent SMAC mimetic (SM), efficiently reactivates latent HIV expression in T cell line models and enhances active caspase 3 expression, a condition that typically leads to apoptosis. In primary CD4⁺ T cells infected with a dual reporter-encoded HIV, APG-1387 decreases latently infected cells without a notable effect on productively infected cells. In virally suppressed humanized (hu)-BLT mice, APG-1387 augments cell-associated viral RNA and potently reduces HIV DNA-containing cells without modulating T cell activation or proliferation. Upon antiretroviral therapy (ART) interruption, HIV r

SUBMITTER: Jain J 

PROVIDER: S-EPMC11699618 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature