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

为了响应RFA-MH-21-170，我们建议扩大和加强长期的科学资源， CNS HIV抗逆转录病毒效应研究项目。新的纵向资源，CHARTER Plus， 将使对艾滋病毒感染者的神经、认知、精神和药物使用障碍的研究成为可能 (PWH)在他们的一生中。该资源将以反映联合国优先事项的科学主题为指导， 艾滋病研究办公室和资助机构。通过结合广泛的评估， 研究领域标准（RDoC）框架和收集多个生物标本（包括 CHARTER Plus将为对抗神经HIV提供无与伦比的武器。批准 请求者将从资源中获得数据、生物标本和科学专业知识，以支持创新 research.为了扩展现有的丰富资源，我们建议对500名成年人进行全面评估 五年内两次队列将包括四个亚组：1）200名PWH， 2）100间新威尔斯亲王医院 在过去10年内诊断出患有抑制性抗逆转录病毒疗法（ART）; 3）100名新的无艾滋病毒感染者 （PWoH）具有可比的人口统计学和风险行为特征，包括药物使用;以及4）100名新 50岁以上的PWoH，特别是阿尔茨海默病和相关疾病风险升高的患者。 这些分组结合起来，将使资源的用户能够解决许多关键的知识差距， 目前在神经艾滋病领域。我们的纵向评估将使用基于领域的认知，行为， 情绪和神经精神评估，映射到RDoC框架。评估还将包括 神经医学数据;药物使用特征;机制生物标志物，病毒和宿主遗传数据，包括 艾滋病毒活动的指标;和神经成像的一个子集的200参与者。宪章协调股 将为研究操作提供中心支持，包括人员培训和认证;协调 招募、评估和保留;数据录入、储存和质量控制/保证;以及生物标本 管理我们在管理CHARTER和处理调查员请求方面有近20年的历史 与国家神经艾滋病组织联盟（NNTC）数据协调中心（DCC）合作， 我们从一开始就在努力对这一资源的需求是明确的。尽管治疗方法的进步 虽然威尔斯亲王医院对他们有很大的裨益，但他们的健康状况仍然受到严重影响;他们经历了医疗， 神经和精神残疾比PWO更常见。专家们争论这些穷人是否 艾滋病毒本身、其免疫效应、过早衰老、 药物使用，或这些因素和其他因素的组合。这些疾病背后的生物学机制 目前，抗逆转录病毒治疗的定义尚不完全，除抗逆转录病毒治疗外，还严重缺乏有效的治疗方法。拟议资源 对RFA-MH-21-170反应良好，将成为推进未来神经HIV研究的关键工具。

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.