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

为响应RFA-MH-21-170，我们建议扩大和加强一个历史悠久的科学资源，即 CNS HIV抗逆转录病毒效应研究(CHECURE)项目。新的纵向资源Charge Plus， 将使对困扰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)在他们的寿命内。该资源将以科学主题为指导，这些主题反映了 艾滋病研究办公室和资助机构。通过结合广泛的评估，专注于 研究领域标准(RDoC)框架和多种生物样本的收集(包括 脑脊液)，Charge Plus将在对抗神经性艾滋病毒方面提供无与伦比的武器。核可 申请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 研究。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。队列将由四个小组组成：1)200名威尔斯亲王医院的患者 特许经营近20年，之前进行过全面评估；2)新建威尔斯亲王医院 在过去10年内确诊接受抑制性抗逆转录病毒疗法(ART)；3)新增100名未感染艾滋病毒的人 (PWoH)具有类似的人口统计和危险行为特征，包括吸毒；以及4)100个新的 年龄在50岁以上的老年人，特别是那些阿尔茨海默病和相关疾病风险较高的人。 结合起来，这些子组将使资源的用户能够解决许多关键的知识差距， 目前存在于神经艾滋病毒领域。我们的纵向评估将使用基于领域的认知、行为、 映射到RDoC框架的情感、和神经精神评估。评估还将包括 神经医学数据；药物使用特征；机械生物标记物、病毒和宿主遗传数据，包括 艾滋病毒活动指标；以及对200名参与者的神经成像。宪章协调股 将为研究工作提供中央支持，包括人员培训和认证；协调 征聘、评估和保留；数据录入、存储和质量控制/保证；以及生物检疫 管理层。我们在管理包机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，与 我们从一开始就致力于此。对这种资源的需求是显而易见的。即使治疗上的进步 对威尔斯亲王医院有很大好处的，他们的健康状况仍然明显受损；他们经历了医疗， 神经性和精神性残疾比PWoH更常见。专家们争论这些穷人是否 结果由艾滋病毒本身、其免疫效应、过早衰老、共同条件等因素造成 吸毒，或这些因素和其他因素的组合。支持这些疾病的生物学机制 仍然没有完全的定义，除了艺术之外的有效疗法也非常缺乏。建议的资源 对RFA-MH-21-170反应良好，将成为推进未来神经艾滋病毒研究的关键工具。

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.