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

CHARTER Plus：艾滋病毒感染者和药物使用障碍患者整个生命周期神经功能和心理健康的前沿研究资源

• 批准号: 10403811
• 负责人: RONALD J. ELLIS
• 金额: $ 205.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10403811
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Address; Adult; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Area; Behavioral; Behavioral Sciences; Biological; Biological Markers; Biological Specimen Banks; Blood; Blood Vessels; Cerebrospinal Fluid; Certification; Characteristics; Cognitive; Collaborations; Collection; Communication; Consultations; Data; Data Analyses; Data Coordinating Center; Dementia; Development; Diagnosis; Disease; Drug Use Disorder; Drug usage; Elderly; Emotional; Equipment and supply inventories; Ethnic Origin; Evaluation; Family history of; Feces; Funding Agency; Future; Genetic; HIV; HIV Infections; HIV antiretroviral; HIV diagnosis; HIV therapy; Human Resources; Immunologics; Immunology; Impaired cognition; Incidence; Inflammation; Knowledge; Life; Link; Logistics; Long-Term Effects; Longevity; Machine Learning; Maps; Medical; Mental Depression; Mental Health; Mental disorders; Methods; National Institute of Mental Health; National NeuroAids Tissue Consortium; Nervous System Physiology; Neuraxis; Neurologic; Outcome; Participant; Persons; Phenotype; Premature aging syndrome; Publishing; Quality Control; Race; Recording of previous events; Research; Research Design; Research Domain Criteria; Research Personnel; Research Priority; Research Support; Resources; Risk; Risk Behaviors; Saliva; Ships; Site; Spinal Puncture; Subgroup; Substance Use Disorder; Therapeutic; Time; Training; Urine; Viral; Work; antiretroviral therapy; base; biopsychosocial; co-infection; cognitive disability; cohort; comorbidity; comparison group; data management; data repository; disability risk; effective therapy; experience; fight against; health disparity; healthspan; improved; innovation; meetings; neuroAIDS; neurobehavioral; neuroimaging; neuropsychiatry; operation; peer; pre-exposure prophylaxis; premature; prevent; psychiatric disability; quality assurance; recruit; response; senescence; sex; syndemic; tool; virology; weapons; web portal

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.

为了回应 RFA-MH-21-170，我们建议扩大和加强长期的科学资源，即 CNS HIV 抗逆转录病毒效应研究 (CHARTER) 项目新的纵向资源 CHARTER Plus， 将使研究困扰艾滋病毒感染者的神经、认知、精神和药物使用障碍成为可能 (PWH) 的整个生命周期，该资源将以反映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结合广泛的评估。 研究领域标准 (RDoC) 框架和多个生物样本的收集（包括 脑脊液），CHARTER Plus 将为对抗神经艾滋病毒提供无与伦比的武器。 请求者将从资源中接收数据、生物样本和科学专业知识，以支持创新 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。 该队列将在五年内进行两次，由四个亚组组成：1) 200 名在 CHARTER 近二十年且之前进行过全面评估；2) 100 名新感染者 过去 10 年内被诊断出接受抑制性抗逆转录病毒治疗 (ART) 3) 100 名未感染 HIV 的新人； (PWoH) 具有可比较的人口和风险行为特征，包括吸毒和 4) 100 个新的； 50 岁以上的 PWoH，特别是那些患阿尔茨海默病和相关疾病的风险较高的人。 这些子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 框架的情绪和神经精神评估也将包括。 神经医学数据；药物使用特征、机械生物标志物、病毒和宿主遗传数据，包括 HIV 活动指标；以及 200 名参与者的神经影像学检查。 将为研究活动提供中央支持，包括人员的培训和认证； 招募、评估和保留；数据输入、存储和质量控制/保证和生物样本； 我们在管理 CHARTER 和处理调查员请求方面拥有近 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， 尽管治疗取得了进展，但我们自成立以来一直在努力。 已经使感染者受益匪浅，但他们的健康寿命仍然受到明显影响； 神经和精神疾病比 PWoH 更常见 专家们争论这些穷人是否。 HIV本身的结果、其免疫效应、过早衰老、综合症，例如 药物使用或这些因素和其他因素的组合导致这些疾病。 仍然不完全定义，而且非常缺乏 ART 之外的有效疗法。 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。