CHARTER Plus: A resource for cutting-edge research on neurological function and mental health in people with HIV and substance use disorders across the lifespan

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In response to RFA-MH-21-170, we propose to expand and enhance a longstanding scientific resource, the CNS HIV Antiretroviral Effects Research (CHARTER) project. The new longitudinal resource, CHARTER Plus, will enable research on the neurologic, cognitive, psychiatric, and drug use disorders that afflict people with HIV (PWH) across their lifespan. The resource will be guided by scientific themes that reflect the priorities of the Office of AIDS Research and the funding agencies. By combining extensive assessments that focus on the Research Domain Criteria (RDoC) framework and the collection of multiple biospecimens (including cerebrospinal fluid), CHARTER Plus will provide an unparalleled weapon in the fight against neuroHIV. Approved requestors will receive data, biospecimens, and scientific expertise from the resource to support innovative research. To extend the existing rich resource, we propose to comprehensively assess a cohort of 500 adults twice over five years. The cohort will consist of four subgroups: 1) 200 PWH who have been followed in CHARTER for nearly two decades and previously underwent comprehensive assessments; 2) 100 new PWH diagnosed within the past 10 years on suppressive antiretroviral therapy (ART); 3) 100 new people without HIV (PWoH) with comparable demographic and risk behavior characteristics, including drug use; and 4) 100 new PWoH older than 50 years, particularly those at elevated risk for Alzheimer’s disease and related disorders. Combined, these subgroups will enable users of the resource to address many of the key knowledge gaps that currently exist in the neuroHIV field. Our longitudinal evaluations will use domain-based cognitive, behavioral, emotional, and neuropsychiatric assessments that map onto the RDoC framework. Assessments will also include neuromedical data; drug use characterization; mechanistic biomarkers, viral and host genetic data, including indicators of HIV activity; and neuroimaging on a subset of 200 participants. The CHARTER Coordinating Unit will provide central support of study operations including training and certification of personnel; coordination of recruitment, assessments, and retention; data entry, storage, and quality control/assurance; and biospecimen management. We have a nearly 20-year history of managing CHARTER and processing investigator requests in collaboration with the National NeuroAIDS Tissue Consortium (NNTC) Data Coordinating Center (DCC), with which we have worked since its inception. The need for this resource is clear. Even though therapeutic advances have greatly benefitted PWH, their healthspan remains markedly compromised; they experience medical, neurological, and psychiatric disabilities much more frequently than PWoH. Experts debate whether these poor outcomes result from HIV itself, its immunological effects, premature senescence, syndemic conditions such as drug use, or combinations of these and other factors. The biological mechanisms underpinning these disorders remain incompletely defined, and effective therapies beyond ART are sorely lacking. The proposed resource responds well to RFA-MH-21-170 and will be a critical tool for advancing future neuroHIV research.