IMPAACT 2015 - Evaluation of the HIV-1 Reservoir in the Central Nervous System of Perinatally-Infected Youth and Young Adults With Cognitive Impairment

Inclusion Criteria: * 13-24 years of age (inclusive) at enrollment (i.e., on the day the participant is enrolled in the study) * Spoken fluency in English or Spanish * If not of legal age to provide independent informed consent: Parent or legal guardian, or other legally authorized representative is willing and able to provide written informed consent for study participation and potential participant is willing and able to provide written assent for study participation * If of legal age but not able to provide independent informed consent due to cognitive impairment as determined by site standard operating procedures (SOPs) and consistent with site institutional review board/ethics committee (IRB/EC) policies and procedures: Parent, legal guardian, or other legally authorized representative is willing and able to provide written informed consent for study participation and potential participant is willing and able to provide written assent for study participation * If of legal age and able to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures: Willing and able to provide written informed consent for study participation * Has confirmed perinatal HIV-1 infection - with no documented evidence to suggest another route of transmission - based on review of available medical records * Has been taking combination ART comprised of at least three agents from at least two classes of antiretroviral therapy for at least 12 consecutive months prior to enrollment as determined by the site investigator or designee based on participant or parent/guardian report and available medical records; regimen changes within the 12 months prior to enrollment are permitted, provided the virologic requirements in criterion below are met * Has at least two consecutive documented plasma HIV-1 RNA values less than 40 copies/mL, at least three months apart, in the 12 months prior to enrollment; one of these values must be based on testing of a specimen collected within the 60 days prior to enrollment * Has a Fluid Cognition Composite Score at least one-and-a-half standard deviations below the published normative mean (i.e., less than 78) based on administration of the NIH Toolbox Cognition Battery Exclusion Criteria: * Any ART interruption for more than seven consecutive days in the 12 months prior to enrollment * Any HIV-1 RNA value greater than 200 copies/mL in the 12 months prior to enrollment * Completed any of the NIH Toolbox subtests specified within 90 days prior to screening * Any documented full scale intelligence quotient (IQ) score more than three standard deviations below the published normative mean (i.e., less than 55) or a Fluid Cognition Composite Score more than three standard deviations below the published normative mean (i.e., less than 55) based on administration of the NIH Toolbox Cognition Battery at screening * Any documented diagnosis of autism spectrum disorder, schizophrenia, or other psychotic disorder * Any known prior infection of the CNS that may be persistent or recurrent (e.g., cryptococcal meningitis, neurosyphilis) * Any known non-HIV-related cause or significant contributing factor for cognitive impairment (e.g., birth injury, head injury, stroke, major or mild neurocognitive disorder due to a condition other than HIV) per Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-V) criteria * Any known or suspected current contraindication to lumbar puncture * Any current sensory or motor impairment severe enough to preclude participation in study evaluations (e.g., blindness, lack of upper limb control) * If female and of reproductive potential (defined as having experienced menarche and having no documented history of a sterilization procedure), known or suspected pregnancy * Any serious or otherwise clinically significant infection of the CNS or bloodstream (other than HIV-1 infection) within 30 days prior to enrollment * Any live vaccine received within 30 days prior to enrollment * Any other (non-live) vaccine received within 7 days prior to enrollment * Received prolonged (more than 14 days) or high dose immunosuppressants within 30 days prior to enrollment (high dose would include \>1 mg/kg prednisone (or equivalent) or any biologic immunosuppressant such as monoclonal antibody based therapy) * Ever received any medication or other approved or investigational agent that may impact HIV-1 reservoirs, including but not limited to: HIV-1 vaccines, HIV-1 gene therapies, Anti-HIV-1 broadly neutralizing antibodies (e.g., VRC01), Anti-PD-1 or anti-PD-L1 antibody, Histone deacetylase inhibitors (e.g., vorinostat, romidepsin, panobinostat), Toll-like receptor agonists, Cytotoxic chemotherapies, Roxolitinib, and Sirolimus