Summary Despite the gains in clinical management, HIV-1 infection is still a life-long disease characterized by reservoirs harboring proviral DNA in a latent/persistent state and occasional clinical complications associated with long- term infection. Because of these therapy-refractile reservoirs, the course of HIV-1 disease is subject to a number of comorbidities, including substance abuse, the aging process, and a host of secondary infections and clinical conditions. Another pressing problem in the HIV-1-infected population is the development of HIV- associated neurologic disorders (HAND) with associated cognitive impairment following HIV-1 brain penetration, which likely serves as a critical reservoir that develops in a vast majority of individuals despite therapy. Given these observations, investigators within and outside of CNAC have been using the Clinical and Translational Research Support Core (CTRSC) resources to address questions relative to: (1) development of a genetic-based strategy directed toward the elimination of HIV-1 to cure HIV/AIDS, (2) understand the genetic makeup of the virus that remains in an ART-controlled patient and in the cellular reservoirs including the brain, (3) design of gRNAs to deliver precise and personalized excision technology, (4) how ART is changing the presentation and severity of neuropsychological impairment, (5) biomarkers that may link to and be underlying mechanisms of HAND, and (6) how selected immune modulators may alter viral reservoir formation and/or affect immune activation and inflammation that underlie chronic HIV disease and HAND. The CTRSC will coalesce resources at two major Universities to build the expanded research support enterprise now designated the Drexel/Temple CNS AIDS Research and Eradication Study (CARES) Cohort. The Drexel/Temple CTRSC will involve the use of the Drexel/Temple CARES Cohort as well as the extensive experience of CTRSC investigators in bridging both the basic science and translational research during the past decade at Drexel and Temple to serve investigators within and outside the CNAC. Because of the unique two-site design for patient recruitment, a parallel leadership structure has been developed and used to oversee research support activities in the CTRSC. The Core Aims will be focused on (1) Clinical Medicine and Database Management; (2) Cognitive Performance and Neuropsychology; (3) Virology, Immunology, and Immune Activation; and (4) Viral Genetics, Genomics, and Bioinformatics. Overall, efforts will focus on providing patient samples and a well-characterized clinical data management system with a wealth of biologic, immunologic, virologic, and genomic data that will facilitate NIH-supported investigations at Temple/Drexel, as well as the projects funded by the Developmental Core. The CTRSC will also provide clinical samples as well as cellular and molecular reagents and bioinformatic information to facilitate research support provided in the Basic Science Core.