PROJECT SUMMARY/ABSTRACT Interdisciplinary clinical research on the combined effects of substance abuse and HIV disease on the central nervous system (CNS) is of considerable public health importance. Despite this, few laboratories address this critical topic and the current training program is the only one dedicated to preparing the next generation of investigators to conduct this research. In this proposed second renewal of our NRSA T32 training grant, “Training in Research on Addictions in Interdisciplinary NeuroAIDS (TRAIN),” we aim to accelerate our contribution to the field. We will continue to recruit talented and diverse pre- and post- doctoral trainees whose academic development will be furthered by an accomplished multidisciplinary team of mentors and the extensive academic resources at UC San Diego. TRAIN has been highly successful in the current funding period–since 2016, the 8 trainees produced 55 research manuscripts (22 first-authored), 88 conference presentations, and 6 book chapters, as well as 2 extramural NIH-funded grants (1 under review, impact score=21, 2nd percentile), 3 supplements to NIH-funded grants, and 2 intramural pilot grants. In this second renewal, we plan to enhance our training grant by augmenting faculty expertise, didactics, and training in new methodologies to support our new complementary theme of the complex biological mechanisms underlying the CNS consequences of HIV and substance use. Factors of particular focus include the microbiome and gut brain-axis, systemic and CNS inflammation, neuroimmunology, and biomarkers. This focus will augment TRAIN continuity themes of neurobehavioral functioning (e.g., frontal systems behaviors, decision-making, memory) and health-related everyday functioning (e.g., treatment adherence, vocational outcomes). Given our previous success and the growing demands of the field, we propose to increase our steady state number of trainees to four pre- and three post-doctoral trainees. Our students and fellows will be actively engaged in individualized career development plans, such as applied research training, didactics, and targeted clinical experiences. TRAIN faculty, all with strong training interests and robust histories of collaborative research, consists of 25 primary mentors across multiple academic levels and disciplines, with considerable expertise across the aforementioned scientific themes. We also have made organizational enhancements (e.g., addition of internal TRAIN committees) to further ensure continued progress towards the accomplishment of trainee goals. TRAIN is led by R. Heaton, Co- Directors I. Grant and D. Moore (new to this role), and Associate Directors J. Iudicello and E. Morgan; this team will oversee all training, scientific, and administrative aspects of the program. TRAIN will be housed at the HNRP-CMCR within the Department of Psychiatry, which is a resource-rich research and training environment in substance abuse and neuroHIV research. Our central g...