HIV-1-infectionPhase 2NCT07081763
Immunotherapy With Baricitinib and Sirolimus, Alone and in Combination, for the Control of HIV-1 Replication After Antiretroviral Treatment Interruption
A Phase 2 study testing Baricitinib 2 MG and Sirolimus 2 MG in people with HIV-1-infection, run by ANRS, Emerging Infectious Diseases.
Trial summary
Natural HIV controllers (HICs) and post-treatment controllers (PTCs) are rare examples of people living with HIV (PLWH) who achieve control of HIV replication without the need for antiretroviral therapy (ART). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- Baricitinib 2 MG and Sirolimus 2 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 191 participants
- Where
- No sites listed yet
- Study dates
- May 2027to May 2033
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≤ 18 years and ≥ 65 years,
- Weight ≥ 50 kg and ≤ 100 kg,
- HIV-1 infection having been diagnosed at primary infection stage with an HIV-1 RNA VL > 1,000 copies/mL and either a negative or incomplete WB [0-5] bands or IB [0-3] bands and/or a previous negative HIV-1 ELISA within the past 3 months,
- Having initiated ART within 2 months of primary HIV-1 infection diagnosis,
- Having received ART continuously without interruption,
- Receiving ART for at least 1 year prior to enrollment,
Show all 16Show fewer
- Receiving DTG-, BIC-, RAL-, or RPV-based ART (PI-, EVG/c-, NVP-, EFV-, ETR- or DOR-based ART must have been switched to DTG-, BIC-, RAL-, or RPV-based ART at W-8).
- Sustained HIV-1 plasma viral load ≤ 50 copies/mL for ≥ 6 months prior to enrollment (with at least two measurements, including the screening value),
- Blood CD4 T-cell count ≥ 500 cells/µL (on the last two measurements, including screening),
- Willing to interrupt ART for ATI and change ART regimen before if required to avoid drug-drug interactions,
- Willing to take valaciclovir 500 mg QD from W0 to W10 to prevent recurrence of herpes or herpes zoster,
- If sexually active, willing to use a reliable method of reducing the risk of transmission to their sexual partners during treatment interruption (condoms or PrEP for their sexual partners).
- If able to have children, willing to use a highly effective method of contraception (combined oral contraceptive pill; implanted contraceptive device, IUD/IUS; physiological or anatomical sterility for self of partner); willing to undergo blood bHCG at screening and before ATI.
- Willing to comply with visit schedule and provide blood samples according to the protocol.
- Written informed consent (at the latest on the day of the enrollment visit and before any exams to be performed in the context of the trial) (article L1122-1-1 of the French CSP).
- Participant covered by Health Insurance (article L1121-11 of the French CSP).
Who cannot join
- HIV-2 infection,
- Previous interruption of ART,
- Loss of virologic suppression (VL > 200 c/mL) at any time while on effective ART; previous blips of VL between 50 and 200 c/mL allowed, except in the 6 months prior to screening,
- Long-acting ART based on CAB/RPV, lenacapavir, islatravir, or ibalizumab,
- Receiving PI-, EVG/c-, NVP-, EFV-, ETR- or DOR-based ART beyond W-8,
- No other active ARV regimen in addition to the current one,
Show all 23Show fewer
- Pregnant or lactating woman,
- Woman expecting to conceive during the trial period,
- Any medical condition that will contraindicate an interruption of ARV treatment,
- History of coronary artery disease, stroke, or blood clots; thrombophilia,
- High cardiovascular risk (SCORE2 ≥ 7.5% if < 50 years, or ≥ 10% if 50-65 years),
- Active cancer or history of cancer,
- Active opportunistic infection,
- Active or latent tuberculosis (unless prophylaxis has been received in the past); participant must be screened for latent tuberculosis according to routine practice prior to initiation of immunotherapeutic interventions,
- Chronic hepatitis B (positive HBs antigen and/or positive HBV DNA) or past-hepatitis B infection (positive anti-HBc antibodies) or hepatitis C (positive HCV RNA); cirrhosis,
- Treatment with systemic corticosteroids or immunosuppressants currently or within 12 weeks prior to study randomization,
- History of experimental vaccination against HIV,
- Ongoing treatment with strong CYP3A4 inducers or inhibitors,
- History of hypersensitivity to macrolides.
- Laboratory parameters at screening:
- Polynuclear neutrophils <1 G/L; Hemoglobin <10 g/dL; Platelets <100 G/L
- GFR <30 ml/min/1.73m2
- TP <50%; ALAT/ASAT >5x ULN; Bilirubin >3x ULN
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Immunotherapy With a JAK1/JAK2 Inhibitor (Baricitinib) and an mTORC1 Inhibitor (Sirolimus), Alone and in Combination, for the Control of HIV-1 Replication After Antiretroviral Treatment Interruption: a Phase II Multicenter, Multi-arm, Multi-stage, Randomized, Double-blind, Placebo-controlled, Adaptative Trial
Natural HIV controllers (HICs) and post-treatment controllers (PTCs) are rare examples of people living with HIV (PLWH) who achieve control of HIV replication without the need for antiretroviral therapy (ART). Therapeutic strategies that can induce such a phenotype are therefore a key goal in the quest for a remission of HIV infection.
JAK1/JAK2 and mTORC1 are key biological pathways involved in the regulation of HIV-1 transcription and replication, as well as the functional capacities of immune effectors, primarily CD8 T cells (exhaustion status and immunometabolic properties), but also NK cells. Immunotherapeutic interventions using a JAK1/JAK2 inhibitor and an mTORC1 inhibitor, alone or in combination to achieve an additive or synergistic effect, are therefore promising candidates to induce a PTC-like phenotype. The use of combined approaches of immunotherapies with different and potentially complementary effects may increase the likelihood of achieving viral control.
This study aims at evaluating the efficacy and safety of three experimental immunotherapeutic interventions (i.e., baricitinib, a JAK1/JAK2 inhibitor, alone; sirolimus, an mTORC1 inhibitor, alone; or their combination) on viral control following an analytic treatment interruption (ATI) of antiretroviral drugs in PLWH who had initiated ART during primary HIV-1 infection. This randomized clinical trial will use an innovative multi-arm multi-stage adaptive design.
Read the detailed description
This phase II multicenter, multi-stage, randomized, double-blind, placebo-controlled, adaptive clinical trial will evaluate the effect of baricitinib and sirolimus, alone and in combination, on viral control following an analytical treatment intervention (ATI).
The trial will follow an adaptive multi-arm multi-stage (MAMS) design. It will be divided into three stages, two interim stages and one final stage. Recruitment in any arm may be stopped early if, in the opinion of the Independent Data Monitoring Committee (IDMC), an experimental arm is considered to have insufficient efficacy or for safety reasons. The final sample size and study duration will depend on how many arms are continued beyond the interim analyses
Participants will be randomized 1:1:1:1 to either one of 4 arms:
- Arm 1: baricitinib + placebo of sirolimus
- Arm 2: sirolimus + placebo of baricitinib
- Arm 3: baricitinib + sirolimus
- Arm 4: placebo of baricitinib + placebo of sirolimus
- Conditions
- HIV-1-infection
- Being tested
- Baricitinib 2 MG, Sirolimus 2 MG, Placebo of baricitinib 2 MG, Placebo of sirolimus 2 MG
- Keywords
- Antiretroviral Treatment Interruption
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Baricitinib 2 MGDrug
Administered orally at 2 mg QD from W0 to W10.
Sirolimus 2 MGDrug
Administered orally at 2 mg QD from W0 to W10.
Placebo of baricitinib 2 MGOther
Administered orally at 2 mg QD from W0 to W10.
Placebo of sirolimus 2 MGOther
Administered orally at 2 mg QD from W0 to W10.
| Study group | Role | What they receive |
|---|---|---|
| baricitinib + placebo of sirolimus | Experimental | baricitinib : participants will receive a 10-week course of baricitinib from W0 to W10, starting 2 weeks before the ATI period (ARV stop at W2) and ending 8 weeks after (W10). Baricitinib will be administered orally at 2 mg QD from W0 to W10.
placebo of sirolimus : participants will receive a 10-week course of sirolimus placebo from W0 to W10, starting 2 weeks before the ATI period (starting at W2) and ending 8 weeks after (W10). Receives: Drug: Baricitinib 2 MG; Other: Placebo of sirolimus 2 MG |
| sirolimus + placebo of baricitinib | Experimental | sirolimus : participants will receive a 10-week course of sirolimus from W0 to W10, starting 2 weeks before the ATI period (ARV stop at W2) and ending 8 weeks after (W10). Sirolimus will be administered orally at 2 mg QD.
placebo of baricitinib : participants will receive a 10-week course of baricitinib placebo from W0 to W10, starting 2 weeks before the ATI period (starting at W2) and ending 8 weeks after (W10). Receives: Drug: Sirolimus 2 MG; Other: Placebo of baricitinib 2 MG |
| baricitinib + sirolimus | Experimental | baricitinib : participants will receive a 10-week course of baricitinib from W0 to W10, starting 2 weeks before the ATI period (ARV stop at W2) and ending 8 weeks after (W10). Baricitinib will be administered orally at 2 mg QD from W0 to W10.
sirolimus : participants will also receive a 10-week course of sirolimus from W0 to W10, starting 2 weeks before the ATI period (ARV stop at W2) and ending 8 weeks after (W10). Sirolimus will be administered orally at 2 mg QD. Receives: Drug: Baricitinib 2 MG; Drug: Sirolimus 2 MG |
| placebo of baricitinib + placebo of sirolimus | Placebo comparator | Participants will receive a 10-week course of both baricitinib placebo and sirolimus placebo from W0 to W10, starting 2 weeks before the ATI period (starting at W2) and ending 8 weeks after (W10). Receives: Other: Placebo of baricitinib 2 MG; Other: Placebo of sirolimus 2 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome measure is the time to restart of ART due to virological rebound or a clinical decision to restart ART due to CD4 T-cell decline, an AE, or for any other reason
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2025
- Study startMay 2027 (estimated)
- Primary completionMay 2029 (estimated)
- Study completionMay 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by ANRS, Emerging Infectious DiseasesThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 191 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ANRS, Emerging Infectious Diseases
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07081763
- Sponsor's protocol ID
- ANRS 0668s RHIVIERA-03
- Other IDs
- 2025-523118-97-00, 2025
- Status last verified
- Oct 2026
- First submitted
- 11 Jul 2025
- Last updated
- 19 Oct 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 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunotherapy With a JAK1/JAK2 Inhibitor (Baricitinib) and an mTORC1 Inhibitor (Sirolimus), Alone and in Combination, for the Control of HIV-1 Replication After Antiretroviral Treatment Interruption: a Phase II Multicenter, Multi-arm, Multi-stage, Randomized, Double-blind, Placebo-controlled, Adaptative Trial
- ClinicalTrials.gov ID
- NCT07081763
- Acronym / sponsor ID
- ANRS 0668s RHIVIERA-03
- Conditions
- HIV-1-infection
- Keywords
- Antiretroviral Treatment Interruption
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 191 participants (estimated)
- Lead sponsor
- ANRS, Emerging Infectious DiseasesOther government
- Study start
- May 2027 (estimated)
- Primary completion
- May 2029 (estimated)
- Study completion
- May 2033 (estimated)
- First posted
- 23 Jul 2025 (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.
Natural HIV controllers (HICs) and post-treatment controllers (PTCs) are rare examples of people living with HIV (PLWH) who achieve control of HIV replication without the need for antiretroviral therapy (ART). Therapeutic strategies that can induce such a phenotype are therefore a key goal in the quest for a remission of HIV infection.
JAK1/JAK2 and mTORC1 are key biological pathways involved in the regulation of HIV-1 transcription and replication, as well as the functional capacities of immune effectors, primarily CD8 T cells (exhaustion status and immunometabolic properties), but also NK cells. Immunotherapeutic interventions using a JAK1/JAK2 inhibitor and an mTORC1 inhibitor, alone or in combination to achieve an additive or synergistic effect, are therefore promising candidates to induce a PTC-like phenotype. The use of combined approaches of immunotherapies with different and potentially complementary effects may increase the likelihood of achieving viral control.
This study aims at evaluating the efficacy and safety of three experimental immunotherapeutic interventions (i.e., baricitinib, a JAK1/JAK2 inhibitor, alone; sirolimus, an mTORC1 inhibitor, alone; or their combination) on viral control following an analytic treatment interruption (ATI) of antiretroviral drugs in PLWH who had initiated ART during primary HIV-1 infection. This randomized clinical trial will use an innovative multi-arm multi-stage adaptive design.
Detailed description
This phase II multicenter, multi-stage, randomized, double-blind, placebo-controlled, adaptive clinical trial will evaluate the effect of baricitinib and sirolimus, alone and in combination, on viral control following an analytical treatment intervention (ATI).
The trial will follow an adaptive multi-arm multi-stage (MAMS) design. It will be divided into three stages, two interim stages and one final stage. Recruitment in any arm may be stopped early if, in the opinion of the Independent Data Monitoring Committee (IDMC), an experimental arm is considered to have insufficient efficacy or for safety reasons. The final sample size and study duration will depend on how many arms are continued beyond the interim analyses
Participants will be randomized 1:1:1:1 to either one of 4 arms:
- Arm 1: baricitinib + placebo of sirolimus
- Arm 2: sirolimus + placebo of baricitinib
- Arm 3: baricitinib + sirolimus
- Arm 4: placebo of baricitinib + placebo of sirolimus
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| baricitinib + placebo of sirolimus | Experimental | Drug: Baricitinib 2 MG, Other: Placebo of sirolimus 2 MGbaricitinib : participants will receive a 10-week course of baricitinib from W0 to W10, starting 2 weeks before the ATI period (ARV stop at W2) and ending 8 weeks after (W10). Baricitinib will be administered orally at 2 mg QD from W0 to W10. placebo of sirolimus : participants will receive a 10-week course of sirolimus placebo from W0 to W10, starting 2 weeks before the ATI period (starting at W2) and ending 8 weeks after (W10). |
| sirolimus + placebo of baricitinib | Experimental | Drug: Sirolimus 2 MG, Other: Placebo of baricitinib 2 MGsirolimus : participants will receive a 10-week course of sirolimus from W0 to W10, starting 2 weeks before the ATI period (ARV stop at W2) and ending 8 weeks after (W10). Sirolimus will be administered orally at 2 mg QD. placebo of baricitinib : participants will receive a 10-week course of baricitinib placebo from W0 to W10, starting 2 weeks before the ATI period (starting at W2) and ending 8 weeks after (W10). |
| baricitinib + sirolimus | Experimental | Drug: Baricitinib 2 MG, Drug: Sirolimus 2 MGbaricitinib : participants will receive a 10-week course of baricitinib from W0 to W10, starting 2 weeks before the ATI period (ARV stop at W2) and ending 8 weeks after (W10). Baricitinib will be administered orally at 2 mg QD from W0 to W10. sirolimus : participants will also receive a 10-week course of sirolimus from W0 to W10, starting 2 weeks before the ATI period (ARV stop at W2) and ending 8 weeks after (W10). Sirolimus will be administered orally at 2 mg QD. |
| placebo of baricitinib + placebo of sirolimus | Placebo comparator | Other: Placebo of baricitinib 2 MG, Other: Placebo of sirolimus 2 MGParticipants will receive a 10-week course of both baricitinib placebo and sirolimus placebo from W0 to W10, starting 2 weeks before the ATI period (starting at W2) and ending 8 weeks after (W10). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age ≤ 18 years and ≥ 65 years,
- Weight ≥ 50 kg and ≤ 100 kg,
- HIV-1 infection having been diagnosed at primary infection stage with an HIV-1 RNA VL > 1,000 copies/mL and either a negative or incomplete WB [0-5] bands or IB [0-3] bands and/or a previous negative HIV-1 ELISA within the past 3 months,
- Having initiated ART within 2 months of primary HIV-1 infection diagnosis,
- Having received ART continuously without interruption,
Key exclusion criteria (23 listed)
- HIV-2 infection,
- Previous interruption of ART,
- Loss of virologic suppression (VL > 200 c/mL) at any time while on effective ART; previous blips of VL between 50 and 200 c/mL allowed, except in the 6 months prior to screening,
- Long-acting ART based on CAB/RPV, lenacapavir, islatravir, or ibalizumab,
- Receiving PI-, EVG/c-, NVP-, EFV-, ETR- or DOR-based ART beyond W-8,
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 |
|---|---|---|
| Baricitinib 2 MGAdministered orally at 2 mg QD from W0 to W10. | Drug | baricitinib + placebo of sirolimus, baricitinib + sirolimus |
| Sirolimus 2 MGAdministered orally at 2 mg QD from W0 to W10. | Drug | baricitinib + sirolimus, sirolimus + placebo of baricitinib |
| Placebo of baricitinib 2 MGAdministered orally at 2 mg QD from W0 to W10. | Other | placebo of baricitinib + placebo of sirolimus, sirolimus + placebo of baricitinib |
| Placebo of sirolimus 2 MGAdministered orally at 2 mg QD from W0 to W10. | Other | baricitinib + placebo of sirolimus, placebo of baricitinib + placebo of sirolimus |
Primary outcome
The primary outcome measure is the time to restart of ART due to virological rebound or a clinical decision to restart ART due to CD4 T-cell decline, an AE, or for any other reason
Time frame: 26 weeks
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 19 Oct 2026.
Related trials for HIV-1-infection
RecruitingObservational study
Cohort of Women Living With HIV-1 and Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide
HIV (Human Immunodeficiency Virus), Pregnancy
RecruitingPhase 4
A Study to Provide Continued Access to Study Drug to Children and Adolescents Who Have Completed Clinical Studies Involving Gilead HIV Treatments
HIV-1-infection
RecruitingObservational study
Leukapheresis Procedures to Obtain Plasma and Lymphocytes for Research Studies on Antiretroviral Naive HIV-1 Research Participants
HIV
Active, not recruitingPhase 3
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With Biktarvy
HIV-1-infection
Active, not recruitingPhase 2/3
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With a Complicated Regimen (ARTISTRY-1)
HIV-1-infection
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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Baricitinib 2 MG and Sirolimus 2 MG in people with HIV-1-infection, run by ANRS, Emerging Infectious Diseases.
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 16 inclusion and 23 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: opening soon, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Pierre Delobel, PhD (+33 (0)561777508, delobel.p@chu-toulouse.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome measure is the time to restart of ART due to virological rebound or a clinical decision to restart ART due to CD4 T-cell decline, an AE, or for any other reason (time frame: 26 weeks). 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 19 Oct 2026.