Inflammation and Depression in People With HIV

Exclusion Criteria

• •\< 18 years of age or \> 65 years of age
• •Pregnancy or breastfeeding
• •Significant hematological abnormalities at screening (ANC \< 1500, Hgb\<10, platelet\< 100,000)
• •History of progressive multifocal leukoencephalopathy
• •Untreated latent tuberculosis infection (which will be screened for prior to entry)
• •Having taken the following immunosuppressive medications within the past 6 months:
• •1. Oral corticosteroids
• •2. Biologic treatments such as etanercept, infliximab, certolizumab, adalimumab, golimumab, tocilizumab, abatacept, Ustekinumab, ixekizumab, secukinumab, or anakinra
• •3. Cyclophosphamide (or any other cytotoxic agent), belimumab, or anifrolumab (or another anti-interferon (IFN) therapy)
• •4. Rituximab, any other B cell depleting therapies, or intravenous immunoglobulin (IVIg)
• •5. any Janus kinase (JAK) inhibitor
• •History of deep venous thrombosis
• •Cardiovascular disease:
• •1. Coronary artery disease or history of myocardial infarction
• •2. Congestive heart failure with left ventricular ejection fraction ≤40% per American Heart Association guidelines
• •3. Stroke history
• •Hematologic malignancies including lymphoma and leukemia
• •Major surgery within 8 weeks prior to screening or will require major surgery during the study
• •Current or recent (\<4 weeks prior to randomization) clinically serious viral (including coronavirus disease 2019 (COVID-19)), bacterial, fungal, or parasitic infection or any other active or recent infection
• •Symptomatic herpes simplex at the time of randomization
• •Symptomatic herpes zoster infection within 12 weeks prior to randomization
• •History of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement)
• •Positive test for hepatitis B virus (HBV) defined as:
• •1. positive for hepatitis B surface antigen (HBsAg), or
• •2. positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B virus deoxyribonucleic acid (HBV DNA)
• •Hepatitis C virus (HCV) infection (hepatitis C antibody-positive and HCV ribonucleic acid \[RNA\]-positive)
• •Cirrhosis of the liver from any cause
• •Any of the following specific abnormalities on screening laboratory tests:
• •1. alanine transaminase (ALT) or aspartate aminotransferase (AST) \>2 x upper limits of normal (ULN)
• •2. alkaline phosphatase (ALP) ≥2 x ULN
• •3. total bilirubin ≥1.5 x ULN (with the exception of patients on atazanavir, who must have total bilirubin \<2 x ULN)
• •Chronic kidney disease with estimated glomerular filtration rate (eGFR) \<40 mL/min/1.73 m\^2
• •History of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; substance abuse/dependence within 6 months of study entry, as determined by severe combined immunodeficiency (SCID)
• •A positive urine drug screen for illicit drugs at any time during the study excluding marijuana
• •An active suicidal plan as determined by a score \>3 on item #3 on the Hamilton Rating Scale for Depression (HAM-D)
• •An active eating disorder or antisocial personality disorder
• •History of dementia
• •Chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), glucocorticoid containing medications or minocycline within 2 weeks of baseline or at any time during the study
• •Any contraindication for MRI scanning
• •Failure of more than 2 antidepressant trials (at least 6 weeks at recommended dose) in the current episode or 5 antidepressant trials lifetime
• •BMI \>42 (to exclude severe obesity) or at the investigator's discretion based on the patient's ability to fit in the MRI scanner