Safety and Effects of Venetoclax to Reduce HIV Reservoir in Adults Living With HIV on Antiretroviral Therapy

What this Trial Is About

Researchers are evaluating the use of venetoclax, a BCL-2 antagonist, to promote the death of HIV-infected cells and reduce the size of the HIV reservoir in people living with HIV PLWH who are on antiretroviral therapy ART. Despite ARTs success in suppressing HIV replication, it cannot cure HIV due to the persistence of latent virus in certain immune cells. This study aims to assess the safety of venetoclax and its effects on pathways related to cell death, immune function, and HIV persistence, laying the groundwork for future combination studies with latency-reversing agents. Participants will receive venetoclax daily for 14 days followed by a 21-day break, with this 35-day cycle repeated three times. Initially, dose escalation will test 200 mg, 400 mg, or 800 mg once daily for 14 days. After determining the maximum tolerated dose, participants will receive three cycles of venetoclax at this dose, each cycle consisting of 14 days on treatment followed by 14 days off. This is a single-arm study without placebo, focusing on venetoclax monotherapy. During the study, participants will undergo safety monitoring and evaluations of HIV persistence and proapoptotic pathways over 140 days. They will continue their ART regimen throughout. Assessments will include laboratory tests, immune function studies, and HIV RNA measurements to understand the drugs impact. Safety will be closely observed, and participants will be followed throughout the treatment and observation periods to collect comprehensive data on venetoclaxs effects in this population.

Administration of Venetoclax to Promote Apoptosis of HIV-infected Cells and Reduce the Size of the HIV Reservoir Among People Living With HIV on ART