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

Sponsor
ANRS, Emerging Infectious Diseases
Study ID
NCT07081763
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

  • HIV-1-infection

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Baricitinib 2 MG — DRUG
    Administered orally at 2 mg QD from W0 to W10.
  • Sirolimus 2 MG — DRUG
    Administered orally at 2 mg QD from W0 to W10.
  • Placebo of baricitinib 2 MG — OTHER
    Administered orally at 2 mg QD from W0 to W10.
  • Placebo of sirolimus 2 MG — OTHER
    Administered orally at 2 mg QD from W0 to W10.

Study Details

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.

Key Dates

Start date
May 31, 2026
Status verified
Jul 2025
Primary completion
May 31, 2029
Completion
Nov 30, 2030

Study Design

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

Arms

  • Experimental: baricitinib + placebo of sirolimus
    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).
  • Experimental: sirolimus + placebo of baricitinib
    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).
  • Experimental: baricitinib + sirolimus
    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.
  • Placebo Comparator: placebo of baricitinib + placebo of sirolimus
    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).

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 ]

Central Contacts

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