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.
