JHU Center for the Advancement of HIV Neurotherapeutics (JHU CAHN)- Clinical Core

项目摘要-临床核心 在过去的15年里，约翰霍普金斯大学(JH)NIMH P30中心专注于进一步发现和 应用新疗法治疗HIV相关认知障碍，并成功地取得进展 全球神经艾滋病毒研究。在这段时间里，临床核心一直在增长并保持纵向 艾滋病毒携带者(PWH)和匹配的艾滋病毒未感染者的特征良好的队列的参与， 并成功地传播了丰富的表型临床和行为数据、生物标本和分析 为50多项由NIH资助的研究提供专业知识，包括24周的鼻内胰岛素I/II期试点试验 艾滋病毒相关神经认知障碍的治疗。从这些有价值的人类数据中，我们获得了至关重要的 对表现多样的中枢神经系统(CNS)功能障碍的异质性的洞察 认知障碍以及情绪性(情绪包括快感缺乏、社交退缩和焦虑)症状 躯体症状(睡眠)，以及认知治疗反应的不同模式。我们还了解到 与安慰剂相比，鼻腔注射胰岛素24周改善了PWH患者的记忆力和注意力。作为回应，我们小组 很早就转向了治疗开发的新创新模式，即个性化医学 开发和传播算法、患者数据驱动的方法，以选择最佳治疗方法 目的和预测重症肝炎患者的个体化治疗反应。2017年，核心走向导师崛起 在大数据协调和机器学习方面处于领先地位，将临床数据收集范围扩大到 与情绪和焦虑症状相关的行为和自我报告指标，整合了大脑测量，以及 包括对遗传天赋、不适应行为和生活经历的评估。通过这件事 经过努力，临床核心是首批利用NIMH研究领域标准(RDoC)的机构之一 神经艾滋病毒领域的框架，一种将促进精准医学治疗方法的方法 威斯康星医院神经精神并发症。在未来五年内，临床核心将与其他JH合作 作为神经艾滋病毒领域的关键资源，我们的核心和中心以外的其他机构将继续创新。 具体地说，临床核心将支持靶标发现、治疗开发和临床试验方面的项目。 在这个框架的背景下，我们的目标是：1)建立一个资源来提供丰富的表型临床数据，以 支持中枢神经系统功能障碍的关键通路/回路的研究，并为治疗开发提供信息 和在威斯康星医院的应用，2)在RDoC方面为学术神经HIV社区提供咨询服务 实施，3)指导下一代神经艾滋病毒科学家，整合RDoC框架， 以及4)通过多个外展计划吸引和教育威尔斯亲王医院社区。

PROJECT SUMMARY – CLINICAL CORE Over the past 15 years, the Johns Hopkins (JH) NIMH P30 Center focused on furthering discovery and application of novel therapeutics to address HIV-associated Cognitive Disorders, and successfully advanced NeuroHIV research globally. During this time, the Clinical Core has grown and maintained longitudinal participation of a well-characterized cohort of people with HIV (PWH) and matched HIV-uninfected individuals, and successfully disseminated richly phenotyped clinical and behavioral data, biospecimens, and analytical expertise to over 50 NIH-funded studies, including a 24 week Phase I/II pilot trial of intranasal insulin for the treatment of HIV-associated neurocognitive disorder. From these valuable human data, we gained crucial insights into the heterogeneity of central nervous system (CNS) system dysfunction that manifests as varied cognitive impairments as well as affective (mood including anhedonia, social withdrawal & anxiety) symptoms and somatic symptoms (sleep), along with divergent patterns in cognitive treatment response. We also learned that 24 weeks of intranasal insulin vs. placebo improved memory and attention in PWH. In response, our group was early to pivot toward a new model of innovation in therapeutic development, namely a personalized medicine approach developing and disseminating algorithmic, patient data-driven approaches to best select therapeutic targets and predict individual treatment response in PWH. In 2017, the Core moved toward mentoring rising leaders in big data harmonization and machine learning, broadening the clinical data collection to capture behavioral and self-report metrics relevant to mood and anxiety symptoms, integrating brain measurements, and incorporating assessments of genetic endowment, maladaptive behaviors, and life experience. Through this effort, the Clinical Core was among the first to capitalize on the NIMH Research Domain Criteria (RDoC) framework in the NeuroHIV field, an approach that will facilitate precision medicine approaches to treating neuropsychiatric complications in PWH. Over the next five years, the Clinical Core will collaborate with other JH Cores and those outside our Center to continue to innovate as a critical resource in the NeuroHIV field. Specifically, the Clinical Core will support projects in target discovery, therapeutic development, and clinical trials. In the context of this framework, we aim to: 1) Establish a resource to provide richly phenotyped clinical data, to support the study of critical pathways/circuits underlying CNS dysfunction, and inform therapeutic development and application in PWH, 2) Provide consulting services to the academic NeuroHIV community in terms of RDoC implementation, 3) Mentor the next generation of NeuroHIV scientists with integration of the RDoC framework, and 4) Engage and educate the community of PWH through multiple outreach programs.