PROJECT SUMMARY – OVERALL The mission of the JHU NIMH NeuroHIV Center for the past 15 years has been to catalyze and support multidisciplinary high-impact science that addresses the NIH strategic plan for HIV research for addressing comorbidities and complications in people with HIV (PWH). The Center has focused on developing novel treatments to mitigate the impact of cognitive impairment in PWH by capitalizing on the investigative talents of JHU thought leaders as well as its strong translational capabilities in drug discovery and development. The Center has worked to promote NeuroHIV research partnerships within JHU, amongst NIMH HIV Centers and across NIH supported NeuroHIV research programs. Through these interactions, the Center facilitated the discovery of three novel first-in-class therapeutic agents which attracted commercial partners to translate discovered therapeutics into the clinic. With respect to training, the Center has provided infrastructure for mentoring the next generation of diverse NeuroHIV scientists. The Center’s new investigator training pipeline has been extensive, ranging from high school seniors to senior faculty new to NeuroHIV, with a particular focus on training scientists from under-represented minority populations. Most recently, in collaboration with other NeuroHIV Centers, the JHU Center organized and led the highly regarded weekly virtual joint NIMH Center’s Joint NeuroHIV Translational Seminar Series. For renewal, the JHU Center for the Advancement of HIV Neurotherapeutics (JHU CAHN) was reconfigured to be a resource capable of facilitating clinical, biomarker, and translational research that address a broader range of neurological and psychiatric complications in NeuroHIV, not limited to cognitive impairment. This important thematic shift aligns with NIMH’s NeuroHIV related research priorities to foster research that integrates central nervous system (CNS) complications more generally. To accomplish this, we will capitalize on the NIMH Research Domain Criteria (RDoC) framework across the Center’s Clinical, Biomarker and Therapeutic Cores, collaborations, and training efforts. These changes will help pivot JHU CAHN toward a new model of innovation in therapeutic development, namely a personalized medicine approach, developing and disseminating patient data-driven approaches to select therapeutic targets, identify biomarkers, and predict individual treatment responses.