Inhibiting the Anti-apoptotic Factor BCL-2 with Venetoclax at ART Initiation to Reduce the HIV Reservoir: A Randomized Controlled Open-label Trial (The INITIATE Study)

What this Trial Is About

Researchers are investigating a new approach to reduce the hidden reservoir of inactive HIV in people living with HIV-1. Although antiretroviral therapy (ART) keeps the virus suppressed and helps restore the immune system, it cannot cure HIV due to this hidden reservoir in long-lived cells. The study focuses on the drug venetoclax, which targets a protein involved in preventing cell death, aiming to promote the death of these infected cells and reduce the reservoir during the start of ART. This is a Phase 1 randomized clinical trial assessing safety and effects of venetoclax in this context. Participants are randomly assigned to one of two groups: one receives venetoclax 200 mg daily along with starting ART, given during specific periods on days 0-14, 35-49, and 70-84; the other group receives ART alone without venetoclax. Study visits and blood samples occur at various timepoints including days 0, 7, 14, 35, 49, 70, 84, 126, 252, and 365 to monitor effects. The trial runs for one year, during which researchers evaluate how venetoclax impacts the HIV reservoir and cell death pathways. Participants will undergo regular blood tests to measure the safety of venetoclax and the levels of HIV DNA in their CD4+ T cells. Researchers will also assess viral decay and signs of cell death influenced by venetoclax over the year. Safety monitoring and adherence to ART will be maintained throughout the study. The trial aims to understand whether venetoclax can safely reduce the latent HIV reservoir, potentially informing future treatments to limit lifelong ART dependency.

Inhibiting the Anti-apoptotic Factor, BCL-2, at the Time of ART Initiation to Promote Apoptosis of HIV-infected Cells and Restrict the Seeding of the HIV Reservoir (The INITIATE Study)