Inflammation and Depression in People With HIV

Korábbi kezelés

• Untreated latent tuberculosis infection (which will be screened for prior to entry)
• Having taken the following immunosuppressive medications within the past 6 months:
  • Oral corticosteroids
  • Biologic treatments such as etanercept, infliximab, certolizumab, adalimumab, golimumab, tocilizumab, abatacept, Ustekinumab, ixekizumab, secukinumab, or anakinra
  • Cyclophosphamide (or any other cytotoxic agent), belimumab, or anifrolumab (or another anti-interferon (IFN) therapy)
  • Rituximab, any other B cell depleting therapies, or intravenous immunoglobulin (IVIg)
  • any Janus kinase (JAK) inhibitor
• 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 zoster infection within 12 weeks prior to randomization
• A positive urine drug screen for illicit drugs at any time during the study excluding marijuana
• Chronic use of glucocorticoid containing medications or minocycline within 2 weeks of baseline or at any time during the study

Más betegség

• History of progressive multifocal leukoencephalopathy
• History of deep venous thrombosis
• Hematologic malignancies including lymphoma and leukemia
• History of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement)
• Positive test for hepatitis B virus (HBV) defined as:
  • positive for hepatitis B surface antigen (HBsAg), or
  • 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)
• 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)
• An active eating disorder or antisocial personality disorder
• History of dementia
• Failure of more than 2 antidepressant trials (at least 6 weeks at recommended dose) in the current episode or 5 antidepressant trials lifetime

Laborértékek

• Significant hematological abnormalities at screening (ANC < 1500, Hgb<10, platelet< 100,000)
• Cardiovascular disease:
  • Coronary artery disease or history of myocardial infarction
  • Congestive heart failure with left ventricular ejection fraction ≤40% per American Heart Association guidelines
  • Stroke history
• Any of the following specific abnormalities on screening laboratory tests:
  • alanine transaminase (ALT) or aspartate aminotransferase (AST) >2 x upper limits of normal (ULN)
  • alkaline phosphatase (ALP) ≥2 x ULN
  • 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

Életkor

• < 18 years of age or > 65 years of age

Egyéb

• Pregnancy or breastfeeding
• Symptomatic herpes simplex at the time of randomization
• Cirrhosis of the liver from any cause
• An active suicidal plan as determined by a score >3 on item #3 on the Hamilton Rating Scale for Depression (HAM-D)
• Any contraindication for MRI scanning
• BMI >42 (to exclude severe obesity) or at the investigator's discretion based on the patient's ability to fit in the MRI scanner

• HIV infected on continuous antiretroviral therapy (ART) with plasma HIV RNA <200 copies/ml for at least 12 months (on at least two previous clinic visits and confirmed at screening)
• Current cluster of differentiation 4 (CD4+) > 350 cells/microliter for at least twelve months (on at least two previous clinic visits and confirmed at screening)
• A primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) major depression, current, or Bipolar, depressed type as diagnosed by the SCID-V
• Score of ≥10 on the 9-item Patient Health Questionnaire (PHQ-9)
• Off all antidepressant or other psychotropic therapy (e.g. mood stabilizers, antipsychotics, and sedative hypnotics) for at least 4 weeks (8 weeks for fluoxetine) or on a stable psychotropic regimen for at least 4 weeks prior to baseline visit
• Significant anhedonia as reflected by a score ≥ 2 on item #1 of the PHQ-9
• CRP≥2mg/L
• Women of reproductive age will have a negative serum pregnancy test at study entry and both men and women must agree to adequate contraception while