Immunotherapy With Baricitinib and Sirolimus, Alone and in Combination, for the Control of HIV-1 Replication After Antiretroviral Treatment Interruption

NCT07081763 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: ANRS 0668s RHIVIERA-032025-523118-97-00
• Study Type: interventional
• Target: 191
• Locations: 0 countries
• Sites: N/A

Brief 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). 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.

Conditions

HIV-1-infection

Keywords

Antiretroviral Treatment Interruption

Outcome Measures

Primary Outcomes (1)

• 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

  26 weeks

Study Arms (4)

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).

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).

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.

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).

Other: Placebo of baricitinib 2 MG; Other: Placebo of sirolimus 2 MG

Interventions

Baricitinib 2 MG DRUG

Administered orally at 2 mg QD from W0 to W10.

baricitinib + placebo of sirolimus; baricitinib + sirolimus

Sirolimus 2 MG DRUG

Administered orally at 2 mg QD from W0 to W10.

baricitinib + sirolimus; sirolimus + placebo of baricitinib

Placebo of baricitinib 2 MG OTHER

Administered orally at 2 mg QD from W0 to W10.

placebo of baricitinib + placebo of sirolimus; sirolimus + placebo of baricitinib

Placebo of sirolimus 2 MG OTHER

Administered orally at 2 mg QD from W0 to W10.

baricitinib + placebo of sirolimus; placebo of baricitinib + placebo of sirolimus

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• 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).

You may not qualify if:

• 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,
• 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,

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

MeSH Terms

Interventions

baricitinib; Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Pierre Delobel, PhD

CONTACT

+33 (0)561777508; delobel.p@chu-toulouse.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2025
• First Posted: July 23, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): November 1, 2030
• Last Updated: July 23, 2025

Record last verified: 2025-07