The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb.

ABSTRACT: None of the currently used anti-HIV-1 agents can effectively eliminate latent HIV-1 reservoirs, which is a major hurdle to a complete cure for AIDS. We report here that a novel oral BET inhibitor OTX015, a thienotriazolodiazepine compound that has entered phase Ib clinical development for advanced hematologic malignancies, can effectively reactivate HIV-1 in different latency models with an EC50 value 1.95-4.34 times lower than JQ1, a known BET inhibitor that can reactivate HIV-1 latency. We also found that OTX015 was more potent when used in combination with prostratin. More importantly, OTX015 treatment induced HIV-1 full-length transcripts and viral outgrowth in resting CD4(+) T cells from infected individuals receiving suppressive antiretroviral therapy (ART), while exerting minimal to

SUBMITTER: Lu P 

PROVIDER: S-EPMC4828723 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature