AIDS and Aging Research Platform (AARP)

摘要 对艾滋病毒感染者（PLWH）进行有效的抗逆转录病毒疗法（ART）已大大降低了死亡率 导致许多人活到了中年和老年。尽管取得了这一成功，但艾滋病毒携带者的感染率很高， 年龄小于10-15岁的合并症、多发病（>1种主要慢性疾病）和功能下降 比未感染的对照组。老年综合征，如虚弱和福尔斯，在PLWH中越来越普遍。 因此，迫切需要关注艾滋病毒/艾滋病感染者的健康寿命，而不仅仅是死亡率。健康，在 与寿命不同，它被定义为一个人健康而不仅仅是活着的时间。克劳德D。胡椒老 美国独立中心（OAlCs）的建立是为了帮助定义衰老表型， 研究功能随年龄下降的原因、预防和治疗。OAlCs已经开发并 在老龄化方面的功能评估得到验证，但缺乏艾滋病毒专门知识的深度和广度。相比之下， 艾滋病研究（CFARs）在艾滋病毒相关的基础，临床和社会/行为方面拥有无与伦比的专业知识 研究，但缺乏强大的资源和专业知识，在老化生物学，老年临床表型和功能 评估。我们的R24项目，“在艾滋病毒和老龄化的界面发展研究”是为了回应 PA-12-064“跨学科老龄化研究发展的网络和基础设施支持。“通过 在这一R24中，我们成功地将CFAR和OAIC联系起来，以支持高优先重点领域的试点项目， 指导艾滋病毒和老龄化接口的研究人员。我们对这一提案的设想是在这一成功的基础上 深化CFAR和OAIC之间的现有联系，并将网络扩展到包括内森·肖克 卓越中心在衰老的基础生物学（NSC）和麦克奈特脑研究所（MBIs）。通过 将OAIC在衰老功能衰退方面的专业知识与NSC在衰老生物学方面的专业知识结合起来， 功能下降的潜在机制，MBI对年龄相关的认知下降和CFAR的专业知识 我们在艾滋病毒方面的专业知识，我们创造了一种综合方法来推进和加快调查， 艾滋病毒和老龄化的接口，通过以下目的： 目标1。提供具体的培训模式和工具的简要清单，以有效收集数据，改善艾滋病毒 临床护理和结果研究。目标2.采用老年科学方法，为试点研究提供平台 以确定衰老的分子标志与功能衰退之间的联系，以及 老年PLWH中常见的合并症。目标3：开发用于评价干预的基础设施 方法及其在艾滋病毒护理中的应用。目标4。提供教育支持、实施建议和 指导新兴的研究人员建立/推进艾滋病毒和老龄化的研究计划。 这些协同目标利用和扩大了R24中建立的艾滋病毒专门知识的基础设施和密切联系 从老年医学和功能评估专业知识的CFAR OAlCs，并扩大他们与 纳入NSC和MBIs，以加强和加速艾滋病毒和老龄化界面的调查。

ABSTRACT Effective antiretroviral therapy (ART) for people living with HIV (PLWH) has dramatically reduced mortality resulting in many surviving into middle and old age. Despite this success, PLWH experience high rates of comorbidities, multimorbidity (>1 major chronic illness), and functional decline at ages 10-15 years younger than uninfected controls. Geriatric syndromes, such as frailty and falls, are becoming more prevalent in PLWH. Thus, there is an urgent need to focus on the healthspan of PLWH rather than just mortality. Healthspan, in contrast to lifespan, is defined as the time someone is healthy not just alive. The Claude D. Pepper Older American Independence Centers (OAlCs) were established to help define aging phenotypes and advance research into the causes, prevention and treatment of functional decline with age. OAlCs have developed and validated functional assessments in aging, but lack depth and breadth of HIV expertise. In contrast, Centers for AIDS Research (CFARs) have unparalleled expertise in HIV-related basic, clinical and social/behavioral research, but lack robust resources and expertise in aging biology, geriatric clinical phenotypes and functional assessments. Our R24 project, “Developing Research At The Interface Of HIV And Aging” was in response to PA-12-064 "Network and Infrastructure Support for Development of Interdisciplinary Aging Research." Through this R24 we successfully linked CFARs and OAICs to support pilot projects in high-priority focus areas and mentor researchers at the interface of HIV and Aging. Our vision for this proposal is to build on this success deepening the ongoing linkage of CFARs and OAICs and expanding the network to include Nathan Shock Centers of Excellence in the Basic Biology of Aging (NSCs) and the McKnight Brain Institutes (MBIs). By bringing together OAICs expertise on functional decline in aging, with NSC expertise in aging biology and the mechanisms underlying function decline, with MBI expertise on age-related cognitive decline, and CFAR expertise on HIV, we create an integrated approach to advancing and accelerating investigation at the interface of HIV and aging via the following Aims: Aim 1. Provide specific training models and a brief inventory of tools to efficiently collect data to improve HIV clinical care and outcomes research. Aim 2. Using a geroscience approach, provide a platform for pilot studies to determine the links between molecular hallmarks of aging with functional decline, and the development of common comorbidities among aging PLWH. Aim 3. Develop infrastructure for evaluating interventional approaches and their application to HIV care. Aim 4. Provide educational support, implementation advice and mentoring for emerging investigators to establish/advance research programs in HIV and aging. These synergistic aims leverage and expand the infrastructure and close ties built in the R24 of HIV expertise from CFARs with the gerontology and functional assessment expertise within the OAlCs and expand them with inclusion of NSCs and MBIs to enhance and accelerate investigation at the interface of HIV and aging.