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

Inclusion Criteria: * 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). * Participant covered by Health Insurance (article L1121-11 of the French CSP). Exclusion Criteria: * 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, * 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