Actively Recruiting
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)
Led by Thomas Aagaard Rasmussen · Updated on 2026-05-07
38
Participants Needed
2
Research Sites
194 weeks
Total Duration
On this page
Sponsors
T
Thomas Aagaard Rasmussen
Lead Sponsor
G
Germans Trias i Pujol Hospital
Collaborating Sponsor
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
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)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Documented HIV-1 infection
- Age 18-70 years at screening
- CD4+ T cell count greater than 300 cells/µL at screening
- Antiretroviral therapy (ART) naive at screening
- Able to give informed consent
- Willingness to continue ART throughout the study
- Agreement to use condoms during sexual intercourse until fully suppressed on ART (HIV-1 RNA <50 copies/mL)
- Agreement to avoid conception attempts during the study period
You will not qualify if you...
- Current or previous use of BCL-2 antagonists or pro-apoptotic cancer therapies
- Suspected HIV acquisition during active PrEP use
- Any condition requiring venetoclax treatment
- Current use of moderate or strong CYP3A4 inhibitors or HIV protease inhibitors
- Current use of strong inhibitors of the P-gp drug efflux pump
- Use of P-gp substrates with narrow therapeutic index
- Use of strong or moderate CYP3A4 inducers, except occasional moderate inducers
- Receipt of immunomodulating or chemotherapy agents within 28 days before study entry
- Any therapy that may affect study results or suitability
- Known allergy to venetoclax or analogues
- Active AIDS-defining opportunistic infection
- Planned changes to ART regimen during study
- Recent gastrointestinal disease or surgery affecting drug absorption
- Active alcohol or substance use impairing compliance
- Inability or unwillingness to follow study procedures
- History of malignancy or transplantation (except treated basal cell carcinoma)
- Co-infection with active hepatitis B or C
- For cleared hepatitis B, ART must include TDF or TAF
- Liver function abnormalities (AST or ALT >3 times normal)
- Severe liver impairment (Child-Pugh Class C)
- Reduced kidney function (eGFR <50 mL/min)
- Significant heart dysfunction
- Pregnancy or breastfeeding or unwillingness to use contraception if of childbearing potential
- Low platelet or neutrophil counts, low hemoglobin, or CD4+ T cell count below 300 at screening
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 2 locations
1
Infectious Diseases, Q Research
Aarhus, Denmark, 8200
Actively Recruiting
2
Hospital Universitari Germans Trias I Pujol, Department of Infectious Diseases
Badalona, Spain
Actively Recruiting
Research Team
T
Thomas A Rasmussen, Associate professor, MD, PhD
CONTACT
J
Jesper D Gunst, MD, PhD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here