SUMMARY The current human immunodeficiency virus type 1 (HIV-1) pandemic is one where people living with HIV (PWH) have had well-suppressed infection with therapy for prolonged periods of time. This has guided research towards focusing on (i) comorbidities (aging, cardiovascular, cancer, metabolic, and immune activation), (ii) side effects of antiretroviral therapy (ART), (iii) neurocognitive and behavioral disorders (occurs approximately 40% of the time), (iv) social and structural determinants of NeuroHIV disparities, and (v) new therapeutics and cure strategies. All of these areas rely on access to PWH and associated samples from PWH. Given these high- priority areas of research, the Clinical and Translational Research Support Core (CTRSC), led by Dr. Wigdahl, will have as its main SERVICE OBJECTIVE to enroll participants (White, Black, Hispanic and corresponding uninfected participant cohorts) to continue the development of a rich and well-managed clinical population that can provide data, advice, technical expertise, and reagents to address many of these questions. One of the main research themes of this center focuses on latency, reservoirs, and cure strategies including reservoirs like the central nervous system (CNS). As such, there is a pressing need to understand the genetics of the viral reservoir and the genetic nature of the HIV-1 quasispecies in individuals well-suppressed by ART. Immunophenotyping will also be performed to understand the immune response in PWH experiencing the aging process as well as other comorbid conditions including substance abuse. In addition, having longitudinal samples from neuropsychologically well-characterized PWH will facilitate longitudinal investigations involving biomarkers and immune factors underlying neuroHIV. The CTRSC will accomplish these goals by (1) refinement and utilization of the clinical cohort to examine parameters of HIV-1 disease and a number of comorbid factors (Szep/Pirrone), (2) utilizing comprehensive neuropsychological evaluation to characterize the nature, progression, and correlates of neurocognitive impairment in HIV-1 (Schultheis/Devlin), and (3) characterization of virological and immunological parameters (Nonnemacher/ Haddad). The CTRSC will interface with the Central Administrative and Management Core (CAMC) and will work closely in Aims 1 and 2 with the NeuroHIV and Community Partnership and Disparities Core (NHCPDC). It will use the Viral Gene Editing and Bioinformatics Core (VGEBC) for experimental design and informatic support of next-generation sequencing services (Aims 1 and 3) and the Cell Biology and Functional Analyses Core (CBFAC) to help develop cell lines and isolate and develop primary cell populations (Aim 3). Finally, the CTRSC will interact with early-career and established investigators from within and outside the HIV community to develop new research questions and grants using the Developmental and Research Mentorship Core (DRMC) and by providing scientifi...