Safety and Impact of Baricitinib on Cell Surivival Pathways, HIV-1 Reservoir and Inflamation in People With HIV-1

Inclusion Criteria:

• Males and females aged between 18 and 65 years on the day of screening visit.

• Confirmed HIV-1 infection.

• Receiving suppressive cART for at least 2 years (defined as maintained plasma viralload <50 copies/mL, allowing for isolated blips [<200 cop/ml, non-consecutive,representing <20% total determinations]).

• Being on the same cART regimen within at least 4 weeks prior to baseline visit (week 0).

• Willing and able to be adherent to their cART regimen for the duration of the study.

• Willing to comply with the requirements of the protocol and available for follow-upfor the planned duration of the study.

• In the opinion of the clinical Investigator, the candidate has understood theinformation provided and can give written Informed Consent.

• If heterosexually active female of childbearing potential using an effective methodof contraception different from hormonal contraception (intra-uterine device (IUD),anatomical sterility in self or partner or sexual abstinence) from 14 days prior tothe first IMP administration and commit to use it until 3 months after the last IMPadministration. All female candidates of childbearing potential who are not sexuallyactive with men at screening, must agree to utilize an effective method ofcontraception if they become sexually active during the study.

• If female of childbearing potential, willing to undergo urine pregnancy tests at thedesignated time points.

• If positive IgG for varicella zoster, adequate herpes zoster vaccination at least 4weeks prior to week 0 visit.

• Willing to accept blood draws at time points specified in the Schedule of Events.

Exclusion Criteria:

• If female of childbearing potential, pregnant or planning a pregnancy during theentire study or lactating.

• Prior history or clinical manifestations of any physical or psychiatric disorderthat could impair the subject's ability to complete the study.

• Any active AIDS-defining disease or progression of HIV-related disease, exceptcutaneous Kaposi's sarcoma not requiring systemic therapy.

• Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, orresected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal, orpenile intraepithelial neoplasia.

• Systemic treatment for cancer within 1 year of study entry.

• Known hypersensitivity to any component of the IMP formulation, or severe ormultiple allergies to drugs or pharmaceutical agents.

• Potential participant received or plans to receive: i. Licensed live attenuated vaccines within 28 days before or after inflammation andimmune biomarkers visit (weeks 0 and 12).

ii. Other vaccines (eg, tetanus, hepatitis A, hepatitis B, rabies, pneumococcal, recombinant Herpes Zoster, Influenza, COVID-19 vaccines) within 14 days before or after inflammation and immune biomarkers visits (weeks 0 and 12).

• Receipt of blood products within 3 months of study entry.

• Current or recent use (within last 3 months) of interferon or systemiccorticosteroids or other immunosuppressive agents (use on inhaled steroids forasthma or topic steroids for localized skin conditions are permitted).

• Any other current or prior therapy which, in the opinion of the investigator, wouldmake the individual unsuitable for the study or influence the results of the study.

• Prior history of thrombotic events (deep venous thrombosis, pulmonary embolism, orarterial thrombosis) or known inherited prothrombotic disorders (Factor V Leiden,prothrombin G2021A mutation, antithrombin deficiency, protein S deficiency, proteinC deficiency, etc).

• Current use of combined hormonal contraceptives or substitutive hormonal treatment.

• History of any of the following cardiovascular diseases: myocardial infarction,unstable angina, congestive heart failure, uncontrolled arrhythmias, cardiacrevascularization, stroke, uncontrolled hypertension, or uncontrolled diabeteswithin 6 months.

• Current smokers over 10 cigarettes per day or former smokers with a history ofsmoking more than 10 packyears, unless they quit smoking more than 15 years ago.

• Positive hepatitis C IgG, unless confirmed clearance of HCV infection (undetectableplasma viral load, spontaneous or following treatment).

• Chronic hepatitis B, defined as positive hepatitis B surface antigen (HBsAg); orpast hepatitis B, defined as positive hepatitis B core antibody (HBcAb), unless ARTregimen contains FTC/TFV during the study.

• Symptomatic herpes zoster or recurrent genital herpes within 24 weeks, or anyhistory of disseminated herpes simplex, disseminated herpes zoster, ophthalmiczoster, or CNS zoster.

• History of active, past, or latent tuberculosis, confirmed through medical history,clinical records, or a positive TB IGRAs by QuantiFERON test, unless documentedpreventive TB treatment with 6 or 9 months of daily isoniazid, or a 3-month regimenof weekly rifapentine plus isoniazid, or a 3-month regimen of daily isoniazid plusrifampicin.

• Any laboratory abnormalities including:

Hematology

• Hemoglobin <10.0 g/dl,

• Absolute neutrophil count ≤1,000 /mm3,

• Absolute lymphocyte count ≤500 /mm3,

• Platelets >450,000/mm3, Biochemistry

• eGFR <30 ml/min,

• AST > 2.5 x ULN,

• ALT > 2.5 x ULN,