HIV Neurobehavioral Research Center

总体项目摘要/摘要 二十多年来，NIMH P30艾滋病毒神经行为研究中心(HNRC)一直是 神经艾滋病毒领域，支持极大地促进了我们对中枢神经系统的理解的研究 (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 续订申请，我们建议继续支持创新、基础/机械、临床和转换 艾滋病毒、其治疗和共病的研究。这将包括对持久性的研究(例如，前病毒表观遗传学) 和根除中枢神经系统中的艾滋病毒(“治愈”议程)以及肠道微生物群改变在艾滋病毒相关疾病中的作用 中枢神经系统紊乱。长期以来，抑郁障碍在艾滋病毒携带者中非常普遍。 (PWH)，特别是当合并认知障碍时，可能会在许多情况下导致不良后果 公共卫生关切的领域，包括较差的医疗参与度、抗逆转录病毒治疗有效性、 社会参与度和生活质量。同时使用维度和诊断评估方法来 抑郁症和认知，我们的目标是支持识别和表征复杂神经行为的研究 PWH的表型，确定其潜在的生物学机制(例如，炎症、肠道生物失调)，以及 研究它们对重症肝炎危重结局的影响。这些目标将通过利用数据和 来自1200多名具有良好特征的PWH和HIV未感染参与者的登记的生物检疫菌，他们有 在过去的5年里接受了全面的HNRC考试。在建议的续期期间，我们 还将通过每年进行200次全面评估来丰富HNRC数据和生物群落资源 在较简要的半年度评估中被确定为正在经历#年变化的登记处参与者年 神经医学状态、情绪、认知或日常功能。HNRC参与者登记处也将 使用新的参与者注册进行了刷新。总之，这些评估旨在确定生物学上的 PWH神经行为改变的机制及其临床危险因素和 结果，以期为今后的干预措施提供信息。此次续签建立在 HNRC作为国内和国际的领导者和促进发病机制研究的资源， PWH神经行为障碍的现象学、治疗和预防。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、微生物组和 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，一个发展核心 将支持创新的试点研究并协调培训机会，以帮助推动下一代的职业生涯 一代神经艾滋病毒科学家。

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.