HIV-1Phase 1INITIATENCT07481175
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)
A Phase 1 study testing Venetoclax in people with HIV-1, run by Thomas Aagaard Rasmussen at 2 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV-1
- What is being tested?
- Venetoclax
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 13 Apr 2026to Jan 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented HIV-1 infection
- Age 18-70 years (both included) at screening
- CD4+ T cell count >300/µL at screening
- ART naïve at screening
- Able to give informed consent
- Ability and willingness to provide informed consent and to continue ART throughout the study
- All participants must agree to use condoms during all sexual intercourse in situations where HIV transmission may still occur, i.e. until fully suppressed on ART (plasma HIV-1 RNA <50 copies/mL)
- All participants must agree not to participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization, egg donation) during the study
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study.
- Current or previous use of a BCL-2 antagonist or other pro-apoptotic agent used as cancer therapy
- Evidence of or strong suspicion that HIV infection was acquired during active PrEP use
- Any concomitant disease where venetoclax treatment is indicated
- Current use of any moderate or strong CYP3A4 inhibitors (such as ketoconazole, voriconazole, posaconazole, itraconazole, ritonavir, cobicistat and clarithromycin)
- Current use of any HIV protease inhibitor (due to CYP3A4 inhibition)
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- Current use of any strong inhibitor of the P-gp drug efflux pump (this includes cobicistat, ritonavir, azithromycin and clarithromycin)
- Current use of P-gp substrates with narrow therapeutic index (such as such as digoxin, tacrolimus, cyclosporine, sirolimus, dabigatran, colchicine, loperamide)
- Current use of strong or moderate CYP3A4 inducers (such as carbamazepine, phenytoin, rifampicin, St. John's wort, bosentan, efavirenz and etravirine); intermittent use of moderate CYP3A4 inducers such as modafinil and nafcillin may be used but should be avoided as much as possible
- Receipt of immunomodulating agents (excluding immunisation) or systemic chemotherapeutic agents within 28 days prior to study entry
- Any other current or prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study
- Known hypersensitivity to the components of venetoclax or its analogues
- Any evidence of an active AIDS-defining opportunistic infection
- Individuals who intend to modify their ART regimen within the study period
- Current or recent gastrointestinal disease or gastrointestinal surgery that may impact the absorption of the investigational drug
- Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy or procedures
- Unable or unwilling to adhere to protocol procedures
- History of malignancy or transplantation, excluding adequately treated basal cell carcinoma
- Co-infection with hepatitis B defined as HBsAg-positive or Hepatitis C defined as HCV-RNA positive (Individuals with prior hepatitis B or C infection that is now cleared are eligible for enrolment)
- For individuals with isolated anti-HBcAb (cleared hepatitis B), the chosen ART regimen must include TDF or TAF
- Impaired liver function with AST or ALT >3 times upper limit of normal
- Severe hepatic impairment (Class C) as determined by Child-Pugh classification
- Impaired renal function with estimated creatinine clearance (eGFR) <50 mL/min
- Significant cardiac dysfunction
- Women who are pregnant or breastfeeding or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy as specified in the inclusion criteria
- The following laboratory values at screening (lab tests may be repeated, as clinically indicated, to obtain acceptable values before failure at screening is concluded but supportive therapies are not to be administered within the week prior to screening tests): Platelet count ≤100 x109/L, Absolute neutrophil count ≤1.0x109/L, Haemoglobin <10,0 g/dL, CD4+ T cell count <300 cells/uL
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Denmark1 site, 1 recruiting
- Recruiting
Infectious Diseases, Q Research
Aarhus, 8200
Thomas A Rasmussen, Associate Professor, MD, PhD, +4593801394, thomrasm@rm.dk
Jesper D Gunst, MD, PhD, +4523886636, jesdam@rm.dk
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitari Germans Trias I Pujol, Department of Infectious Diseases
Badalona
José M Marhuenda, MD, PhD, +34934657897, jmolto@lluita.org
About this study
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: An Investigator-initiated Randomised, Controlled, Open-label Clinical Trial (The INITIATE Study)
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.
Read more
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
- HIV-1
- Being tested
- Venetoclax
- Keywords
- venetoclax, bcl-2 inhibitor, anti-apoptotic protein
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
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 group | Role | What they receive |
|---|---|---|
| Study participants receive venetoclax 200 mg concurrent with initiating ART | Experimental | Not described Receives: Drug: Venetoclax |
| ART alone | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety endpoint: Determine the safety of venetoclax administration in PLWH at the time of ART initiation
Safety defined as treatment-emerging adverse events (AEs) related to study treatment
Measured: Day 0 to Day 365
Effect endpoint: The frequency of peripheral blood CD4+ T cells containing intact HIV-DNA
The frequency of peripheral blood CD4+ T cells containing intact HIV-DNA using the Cross-Subtype Intact Proviral DNA Assay (IPDA)
Measured: Day 365
Secondary outcomes (2)
Impact on viral decay and HIV persistence of venetoclax administration in PLWH at the time of ART initiation
Measured: Day 0 to Day 365
Impact of venetoclax administered at the time of ART initiation on cellular apoptosis pathways in PLWH
Measured: Day 0 to Day 365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2026
- Study start13 Apr 2026
- Primary completionJan 2030 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thomas Aagaard Rasmussen
- Sponsor type
- University, hospital or other
- Collaborators
- Germans Trias i Pujol Hospital, Walter and Eliza Hall Institute of Medical Research, The Alfred, Aarhus University Hospital
- Responsible party
- Sponsor-investigator, Thomas Aagaard Rasmussen, University of Aarhus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07481175
- Sponsor's protocol ID
- INITIATE-001
- Other IDs
- 2025-521841-26-00, 2025
- Acronym
- INITIATE
- Status last verified
- Apr 2026
- First submitted
- 13 Mar 2026
- Last updated
- 7 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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: An Investigator-initiated Randomised, Controlled, Open-label Clinical Trial (The INITIATE Study)
- ClinicalTrials.gov ID
- NCT07481175
- Acronym / sponsor ID
- INITIATE / INITIATE-001
- Conditions
- HIV-1
- Keywords
- venetoclax, bcl-2 inhibitor, anti-apoptotic protein
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- Thomas Aagaard RasmussenUniversity, hospital or other
- Collaborators
- Germans Trias i Pujol Hospital, Walter and Eliza Hall Institute of Medical Research, The Alfred, Aarhus University Hospital
- Study start
- 13 Apr 2026 (actual)
- Primary completion
- Jan 2030 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 18 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study participants receive venetoclax 200 mg concurrent with initiating ART | Experimental | Drug: Venetoclax |
| ART alone | No intervention | – |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Documented HIV-1 infection
- Age 18-70 years (both included) at screening
- CD4+ T cell count >300/µL at screening
- ART naïve at screening
- Able to give informed consent
Key exclusion criteria (26 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study.
- Current or previous use of a BCL-2 antagonist or other pro-apoptotic agent used as cancer therapy
- Evidence of or strong suspicion that HIV infection was acquired during active PrEP use
- Any concomitant disease where venetoclax treatment is indicated
- Current use of any moderate or strong CYP3A4 inhibitors (such as ketoconazole, voriconazole, posaconazole, itraconazole, ritonavir, cobicistat and clarithromycin)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VenetoclaxVenetoclax 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 | Drug | Study participants receive venetoclax 200 mg concurrent with initiating ART |
Primary outcome
Safety endpoint: Determine the safety of venetoclax administration in PLWH at the time of ART initiation
Time frame: Day 0 to Day 365
Safety defined as treatment-emerging adverse events (AEs) related to study treatment
Effect endpoint: The frequency of peripheral blood CD4+ T cells containing intact HIV-DNA
Time frame: Day 365
The frequency of peripheral blood CD4+ T cells containing intact HIV-DNA using the Cross-Subtype Intact Proviral DNA Assay (IPDA)
2 secondary outcomes
Impact on viral decay and HIV persistence of venetoclax administration in PLWH at the time of ART initiation
Time frame: Day 0 to Day 365
Impact of venetoclax administered at the time of ART initiation on cellular apoptosis pathways in PLWH
Time frame: Day 0 to Day 365
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Venetoclax in people with HIV-1, run by Thomas Aagaard Rasmussen at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thomas A Rasmussen, Associate professor, MD, PhD (004593801394, thomrasm@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2026.