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severe MDD, psychotic disorders, manic or hypomanic symptoms occurring in the context of bipolar disorder type I or II, or cyclothymic disorder, or another current Axis I diagnosis judged by the investigator to interfere with the trial.\n* Study candidate self-report of depressive symptoms that have persisted for over 50 percent of waking hours and for over 50 percent of days over the 24 months prior to study entry.\n* Severe, active alcohol or substance use disorder by DSM-5-TR criteria in the 6 months prior to study entry.\n* Active alcohol or substance use judged by the investigator to interfere with the trial.\n* Any acute infection within 14 days prior to study entry.\n* Acute or serious illness requiring systemic treatment and\u002For hospitalization within 90 days prior to study entry.\n* Active coronary artery disease (CAD) or myocardial infarction (MI) within 180 days prior to study entry.\n* Presence of rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus (SLE), dermatomyositis, ulcerative colitis, Crohn's disease, or other chronic inflammatory conditions.\n* Immune reconstitution inflammatory syndrome (IRIS) or a history of IRIS within 180 days prior to study entry.\n* Unstable or advanced liver disease.\n* Receipt of medications judged by the site investigator to significantly influence depression or neurocognitive function within 30 days prior to study entry.\n* Non-HIV-associated neurological disorder comorbidity.\n* Diagnosis of epilepsy with antiepileptic drug treatment.\n* Untreated HCV infection and HCV viremia.\n* Current CNS malignant tumor or CNS opportunistic infection (OI).\n* Current systemic malignant tumor or of a current systemic AIDS-defining OI.\n* History of completed treatment of CNS or systemic malignant tumor within the 5 years prior to study entry.\n* History of completed treatment of CNS OI within the 5 years prior to study entry.\n* Documented history of completed treatment of systemic AIDS-defining OI, as well as Mycobacterium Tuberculosis Infection, within the 180 days prior to study entry.\n* New diagnosis of syphilis or treatment for syphilis within the 180 days prior to study entry.\n* History of neurosyphilis.\n* Severe chronic obstructive pulmonary disease.\n* Congestive heart failure (CHF).\n* Use of systemic steroids daily (except testosterone).\n* Diseases that cause a known bleeding diathesis.\n* Immunostimulant therapies and trials of non-FDA-approved ARV medications within 30 days prior to study entry.\n* Immunosuppressive medications if judged by the investigator to affect study outcomes.\n* Currently pregnant, planning to become pregnant during the study period, or currently breastfeeding.\n* Known allergy\u002Fsensitivity or any hypersensitivity to the study drugs or their formulations.\n* Study candidates on prohibited medications at the time of screening will be excluded from study participation.\n\nInclusion Criteria for Participants at US Sites Who Consent to the Lumbar Puncture (LP) Procedure:\n\n* Non-focal neurological examination. Study candidates with focal findings should have expert assessment for mass effect prior to the LP.\n* Laboratory values that meet LP protocol criteria as determined by the site investigator.\n\nExclusion Criteria for Participants at US Sites who Consent to the LP Procedure:\n\n* Current use of anti-coagulants.\n* Known presence of intracerebral mass or lesion that is judged to affect the safety of an LP.\n* Known presence of an active CNS infection that could alter CNS\u002FCSF inflammatory measures.\n* Known allergy to lidocaine.\n* Individuals who are unable to safely tolerate an LP due to physical limitation or condition.\n* Body mass index (BMI) greater than 40 kg\u002Fm\\^2.","ALL","18 Years","70 Years",{"count":677,"type":678},186,"ESTIMATED","INTERVENTIONAL",[681],"PHASE2","A phase II, randomized, open-label, two-arm clinical trial evaluating the safety and efficacy of pramipexole extended release (ER) versus escitalopram for the treatment of major depressive disorder (MDD) and comorbid MDD with mild neurocognitive disorder (MND) in persons with HIV (PWH). Participants will be assessed comprehensively and briefly at intercurrent visits to monitor for toxicity, response to therapy, and to assess for dose changes.\n\nAn optional sub-study to evaluate treatment impact on the cerebrospinal fluid (CSF) profile will be conducted in a subset of 36 participants.",[684,685,686],"Major Depressive Disorder","Mild Neurocognitive Disorder","HIV",[688],"Comorbid MND","2026-06-12",{"date":691,"type":692},"2026-06-15","ACTUAL",{"date":694,"type":692},"2026-05-17",{"date":696,"type":678},"2026-12-02",{"name":5,"class":6},41]