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.
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,
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,
Parallel
Baricitinib 2 MG
DrugAdministered orally at 2 mg QD from W0 to W10.
Sirolimus 2 MG
DrugAdministered orally at 2 mg QD from W0 to W10.
Placebo of baricitinib 2 MG
Other interventionAdministered orally at 2 mg QD from W0 to W10.
Placebo of sirolimus 2 MG
Other interventionAdministered orally at 2 mg QD from W0 to W10.
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
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This trial is not recruiting at the moment. You can still explore other options:
