The National Institute of Mental Health (NIMH) and the National Institute of Neurological Disorders and Stroke (NINDS) invite novel research grant applications to address the problem of HIV-1 persistence focused solely on the central nervous system (CNS) of HIV-infected persons treated with Highly Active Anti-Retroviral Therapy (HAART). This Funding Opportunity Announcement (FOA) will support highly innovative research in five areas: (1) basic research to identify and characterize CNS-based cellular reservoirs of HIV-1 for individuals on HAART; (2) basic research to determine the mechanisms involved in the temporal establishment, maintenance, and resurgence of CNS-based HIV-1 reservoirs in relationship to the effects and timing of HAART, viral expression, and viral evolution within the brain; (3) development of physiologically relevant animal models and CNS-based cellular assays that recapitulate HIV-1 persistence and latency in the presence of effective HAART; (4) drug screening of potential agents which traverse the blood-brain barrier and eliminate latent or other sources of residual virus in the CNS; and (5) design of therapeutic strategies aimed at eradication of HIV-1 from the CNS. Applications ranging from basic to translational research in domestic and international settings are of interest. Multidisciplinary research teams are encouraged but not required.