HIV Neurobehavioral Research Center

总体项目总结/摘要 二十多年来，NIMH P30 HIV神经行为研究中心（HNRC）一直是 neuroHIV领域，支持的研究大大推进了我们对中枢神经系统的理解 (CNS)艾滋病毒疾病的后果及其预测因素、预防、诊断和治疗。在这 更新申请，我们建议继续支持创新，基础/机械，临床和转化 艾滋病毒及其治疗和合并症的研究。这将包括持久性研究（例如，前病毒表观遗传学） 和根除CNS中的HIV（“治愈”议程）以及肠道微生物组改变在HIV相关性 CNS疾病。长期以来，人们一直认为抑郁症在艾滋病毒感染者中非常普遍 (PWH)并且，特别是当与认知障碍相结合时，可能导致许多人的不良后果。 公共卫生关注领域，包括医疗保健参与度较差，抗逆转录病毒治疗有效性， 社会参与和生活质量。使用维度和诊断评估方法， 抑郁症和认知，我们的目标是支持研究识别和表征复杂的神经行为 PWH中的表型，确定其潜在的生物学机制（例如，炎症、肠道生态失调），以及 研究它们对威尔斯亲王医院关键结果的影响。这些目标将通过利用数据和 来自1200多名特征良好的PWH和HIV未感染参与者的注册表的生物标本， 在过去5年中接受了HNRC的全面考试。在建议的更新期间，我们 还将通过开展200项综合评估， 在较简短的半年期评估中被确定为正在发生变化的登记册参与方的年份 神经医学状态、情绪、认知或日常功能。HNRC参与者登记处还将 更新了新的参与者注册。总之，这些评价旨在确定生物学 PWH神经行为改变的基础机制，以及其临床风险因素， 结果，以便为今后的干预提供信息。这一更新建立在 HNRC作为国家和国际领导者以及促进发病机制研究的资源， 现象学，治疗和预防PWH的神经行为障碍。为了实现这些目标， 我们提出了四个重新设计的科学核心（神经行为和精神病学，神经医学，微生物组， 神经病毒学和生物学），将大力支持HNRC的目标，并提供智力领导和 技术支持.一个行政核心将支持和协调他们的活动， 将支持创新的试点研究，并协调培训机会，以帮助推动未来的职业生涯 神经艾滋病科学家的一代。

OVERALL PROJECT SUMMARY/ABSTRACT For over two decades, the NIMH P30 HIV Neurobehavioral Research Center (HNRC) has been a leader in the neuroHIV field, supporting research that has greatly advanced our understanding of the central nervous system (CNS) consequences of HIV disease, as well as their predictors, prevention, diagnosis, and treatment. In this renewal application, we propose to continue supporting innovative, basic/mechanistic, clinical, and translational studies of HIV, its treatment, and comorbidities. This will include studies of persistence (e.g., proviral epigenetics) and eradication of HIV in the CNS (“cure” agenda) and the role of gut microbiome alterations in HIV-associated CNS disorders. Depressive disorders have long been recognized to be highly prevalent among persons with HIV (PWH) and, especially when combined with cognitive impairment, may result in adverse consequences in many areas of public health concern, including poorer healthcare engagement, antiretroviral therapy effectiveness, social engagement, and life quality. Using both dimensional and diagnostic assessment approaches to depression and cognition, we aim to support research identifying and characterizing complex neurobehavioral phenotypes in PWH, determining their underlying biological mechanisms (e.g., inflammation, gut dysbiosis), and examining their effects on critical outcomes in PWH. These aims will be achieved by drawing on data and biospecimens from a registry of over 1200 well characterized PWH and HIV-uninfected participants, who have received comprehensive HNRC examinations during the last 5 years. During the proposed renewal period, we also will enrich the HNRC data and biospecimen resource by conducting 200 comprehensive assessments per year of registry participants who are identified on briefer semi-annual assessments as undergoing changes in neuromedical status, mood, cognition, or everyday functioning. The HNRC Participant Registry also will be refreshed with new participant enrollments. Together, these evaluations aim to determine the biological mechanisms underpinning neurobehavioral changes in PWH, as well as their clinical risk factors and consequences, with a view toward informing future interventions. This renewal builds on the track record of the HNRC as a national and international leader and a resource that facilitates research on pathogenesis, phenomenology, treatment, and prevention of neurobehavioral disturbances in PWH. To accomplish these goals, we propose four redesigned Scientific Cores (NeuroBehavioral and Psychiatry, NeuroMedical, Microbiome, and NeuroVirology and Biology) that will strongly support the HNRC aims and provide intellectual leadership and technical support. An Administrative Core will support and coordinate their activities, and a Developmental Core will support innovative pilot studies and coordinate training opportunities to help advance the careers of the next generation of neuroHIV scientists.