Role of T-Cells in HIV CNS Reservoir Seeding, Persistence, and Neuropathogenesis (R21 Clinical Trial Not Allowed)

Eradicating latent reservoirs of HIV-1 within the body and achieving a sterilizing or functional cure have become priority areas in the AIDS field and NIH AIDS programs across many Institutes and Centers, including NIMH. In addition understanding the mechanisms of HIV- associated co-morbidities in the setting of effective anti-retroviral therapy (ART) is a major topic of interest in the field. HIV Associated CNS (central nervous system) co-morbidities continue to exist despite excellent virologic control in this compartment. HIV persistence and neuroinflammation also continues to observed in the CNS in the setting of ART. HIV targets the CNS early in infection, and HIV-infected individuals suffer from mild forms of neurological impairments even under antiretroviral therapy (ART). CD4+ T cells and monocytes mediate HIV entry into the brain and constitute a source for HIV persistence and neuronal damage. CD8+ T cells are also massively recruited in the CNS in acute infection to control viral replication.