NCT07081763

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

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

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 191 (estimated)
• Sponsor: ANRS, Emerging Infectious Diseases · Other Government
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

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

Interventions

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

Timeline

• Start date: 2026-05-01
• Primary completion: 2029-05-01
• Completion: 2030-11-01
• First posted: 2025-07-23
• Last updated: 2025-07-23