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)

Sponsor
Thomas Aagaard Rasmussen
Study ID
NCT07481175
Phase
PHASE1
Status
Recruiting
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Conditions

  • HIV-1

Eligibility Criteria

Sex
ALL
Age
18 Years - 70 Years
Healthy Volunteers
Not accepted

Interventions

  • Venetoclax — DRUG
    Venetoclax 200 mg will be given daily on days 0-14, days 35-49 and days 70-84. Study visits and blood draws will be done at days 0, 7, 14, 35, 49, 70, 84, 126, 252 and 365

Study Details

Combination therapy with antiretroviral medication (ART) has proven effective in keeping HIV suppressed and restoring the immune system, but it cannot cure the infection. Therefore, lifelong treatment is necessary. The reason for this is a reservoir of inactive virus that remains hidden in long-lived cells and cannot be eliminated by either HIV treatment or the immune system. This reservoir is the primary barrier to a cure for HIV and must be minimized or eliminated in order to make it possible to discontinue lifelong ART treatment. Several studies have been conducted with the aim of reducing the reservoir of inactive virus. The drugs used have been able to activate the virus in resting infected cells, thereby making the virus visible to the immune system. Unfortunately, this type of experimental treatment has not been sufficient to reduce the reservoir of inactive HIV in long-lived cells, possibly because these cells do not undergo cell death to a sufficient degree due to specific alterations in the mechanisms of cell death signaling. The drug venetoclax (Venclyxto) is an inhibitor of BCL-2 (B Cell Lymphoma-2), a key factor involved in the regulation of programmed cell death. Studies have shown increased BCL-2 activity in long-lived cells infected with HIV. In laboratory experiments, we have demonstrated that treating cells with venetoclax while simultaneously activating HIV can lead to the elimination of HIV-infected cells. In experiments with HIV-infected humanized mice receiving ART, we further found that treatment with venetoclax delayed viral rebound after interruption of ART compared with mice that were not treated with venetoclax. The purpose of this study is to investigate whether treatment with venetoclax in people with HIV who are initiating HIV therapy can promote the death of latently infected cells and thereby lead to a reduction in the latent HIV reservoir. The study will examine the safety and the effect of venetoclax.

Key Dates

Start date
Apr 13, 2026
Status verified
Apr 2026
Primary completion
Jan 31, 2030
Completion
Jan 31, 2030

Study Design

Enrollment
38 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Study participants receive venetoclax 200 mg concurrent with initiating ART
  • No Intervention: ART alone

Primary Outcome Measure

Safety endpoint: Determine the safety of venetoclax administration in PLWH at the time of ART initiation [ Time Frame: Day 0 to Day 365 ]

Central Contacts

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