The Impact of HIV and Aging on Physical Function and the Somatopause.

描述(由申请人提供)：这是由Kristine Erlandson医学博士修订的以患者为导向的K23指导职业发展奖的申请。她提议的研究将集中在生长激素轴的紊乱，作为感染人类免疫缺陷病毒(HIV)的成年人身体功能下降的潜在机制。应聘者：Erlandson博士是一名获得董事会认证的内科医生和传染病专家。她目前是科罗拉多大学丹佛-安舒茨医学院传染病和老年医学系的医学助理教授。Erlandson博士寻求在老年医学、内分泌学/新陈代谢和传染病方面的研究培训，这样她就可以发展研究艾滋病毒感染中衰老并发症所需的技能。培训：通过实践指导研究、正式课程和会议/研讨会，Erlandson博士的K23职业发展计划将侧重于：1)培养设计和实施前瞻性纵向临床研究的技能；2)学习进行、分析和解释生长激素轴研究，包括睡眠的影响；3)提高衰老研究的知识和技能，包括进行身体功能评估、运动测试和肌肉活检；以及4)加强研究领导能力和扩大研究合作。导师/环境：Erlandson博士组建了一个由导师和顾问组成的团队，在有效研究艾滋病毒老化所需的多个研究学科之间架起桥梁。作为导师，坎贝尔、施瓦茨和布朗博士将在艾滋病毒研究(坎贝尔)、衰老研究(施瓦茨)、生长激素和内分泌学的其他方面(布朗、施瓦茨)、设计和进行纵向临床试验(施瓦茨、坎贝尔和布朗)方面提供专业知识和职业指导。睡眠(Burgess)、荷尔蒙分泌模式统计分析(Carlson)和频繁荷尔蒙采样(Wright)的合作者将在拟议的培训和研究活动中为Erlandson博士提供支持。此外，Erlandson博士还将获得艾滋病临床试验小组的临床研究基础设施、数据管理和统计支持，以实施由艾滋病临床试验小组赞助的临床试验。来自多中心艾滋病队列研究和妇女机构间艾滋病毒研究的艾滋病毒未感染者的储存样本和可靠数据将提供具有类似人口统计和艾滋病毒风险获取因素的对照组。科罗拉多大学将通过科罗拉多临床和翻译科学研究所(由NIH临床转化科学奖支持)、研究生院、公共卫生学院、众多指导、领导和教学机会、为1500多名患者提供护理的艾滋病毒诊所、强大的多学科老年门诊诊所和哈特福德老年卓越中心提供研究支持。研究：与类似的艾滋病毒人群相比，即使在接受有效的抗逆转录病毒治疗的情况下，艾滋病毒患者的发病率和死亡率也过高。接受抗逆转录病毒治疗的人很少死于艾滋病并发症，相反，他们有早发性衰老并发症，包括身体功能受损、16、17、虚弱18-22和跌倒4。胰岛素样生长因子(IGF)-I是肌肉和骨骼中生长激素(GH)的主要介体。在一些老年人群中，低IGF-I与虚弱、骨骼减少(肌肉质量和力量不足)和死亡率有关。在我们接受有效抗逆转录病毒治疗的中年HIV成人队列中，较低的IGF-I与明显更大的功能损害几率相关。根据我们的数据，我们认为GH/IGF-I轴的损害可能是导致HIV衰老并发症的重要途径。利用五个独特的现有队列，拟议的项目将评估IGF-I与艾滋病毒和艾滋病毒成人之间144周的功能损害的纵向联系(目标1)；随机开始抗逆转录病毒治疗后IGF-I的变化(目标2)；以及艾滋病毒和年龄对24小时生长激素分泌模式的影响(目标3)。摘要：这将是第一次评估1)IGF-I与老年HIV成年人身体功能轨迹的关系，2)开始抗逆转录病毒治疗对HIV感染者IGF-I的影响，以及3)感染或不感染HIV的老年人24小时生长激素分泌模式。Erlandson博士实施了这项名为《艾滋病毒和老龄化对身体机能和更年期的影响》的指导性研究和培训建议，这将有助于她发展成为艾滋病毒、成功衰老和身体机能领域的独立研究员和领导者。

DESCRIPTION (provided by applicant): This is a revised application for a K23 Patient-Oriented Mentored Career Development award by Kristine Erlandson, MD. Her proposed research will focus on disturbance in the growth hormone axis as a potential mechanism for physical function decline among human immunodeficiency virus (HIV)-infected adults. Candidate: Dr. Erlandson is a board-certified internist and infectious disease specialist. She is currently an Assistant Professor of Medicine in the Divisions of Infectious Diseases and Geriatric Medicine at the University of Colorado Denver-Anschutz Medical Campus School of Medicine. Dr. Erlandson seeks research training in the disciplines of geriatric medicine, endocrinology/metabolism, and infectious diseases so she can develop the skills needed to investigate complications of aging in HIV infection. Training: Through hands-on mentored research, formal coursework, and conferences/seminars, Dr. Erlandson's K23 career development plan will focus on: 1) developing skills in design and implementation of prospective longitudinal clinical research studies; 2) learning to conduct, analyze and interpret studies of th growth hormone axis, including effects of sleep; 3) improving knowledge & skills for aging research including conduct of physical function assessments, exercise testing, and muscle biopsies; and 4) strengthening research leadership abilities and expanding research collaborations. Mentors/Environment: Dr. Erlandson has assembled a team of mentors and consultants to bridge the multiple research disciplines necessary to effectively investigate aging in HIV. As mentors, Drs. Campbell, Schwartz, and Brown will provide expertise and career guidance in HIV research (Campbell), aging research (Schwartz), growth hormone and other aspects of endocrinology (Brown, Schwartz), design and conduct of longitudinal clinical trials (Schwartz, Campbell, Brown). Collaborators in sleep (Burgess), statistical analysis of hormone secretion patterns (Carlson), and frequent hormone sampling (Wright) will support Dr. Erlandson in the proposed training and research activities. Additionally, clinical research infrastructure, data management, and statistical support of the AIDS Clinical Trials Group will be available to Dr. Erlandson for the implementation of AIDS Clinical Trials Group-sponsored clinical trials. The stored samples and robust data from HIV-uninfected persons from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study will provide a control group with similar demographic and HIV risk acquisition factors. The University of Colorado will provide research support through the Colorado Clinical and Translational Science Institute (supported by the NIH Clinical Translational Sciences Award), the Graduate School, School of Public Health, numerous opportunities for mentoring, leadership, and teaching, an HIV clinic that provides care for over 1500 patients, a robust multi-disciplinary outpatient Senior's Clinic, and the Hartford Center for Geriatric Excellence. Research: In comparison to similar HIV- populations, HIV+ persons, even when on effective antiretroviral therapy, experience an excess of morbidity and mortality. Persons on ART rarely die from complications of AIDS, but instead have early onset of aging complications including impaired physical function5,16,17, frailty18-22, and falls4. Insulin-like growth factor (IGF)-I is the primary mediator of growth hormone (GH) on muscle and bone. Low IGF-I is associated with frailty, sarcopenia (low muscle mass and strength), and mortality in some aging cohorts. In our cohort of middle-aged HIV+ adults on effective ART, lower IGF-I was associated with a significantly greater odds of functional impairment. Based on our data, we believe impairment in the GH/IGF-I axis may be an important pathway leading to aging complications in HIV. Using five unique, existing cohorts, the proposed project will evaluate the longitudinal association of IGF-I with functional impairment over 144 weeks between HIV+ and HIV- adults (Aim 1); the change in IGF-I with randomized initiation of ART (Aim 2); and the impact of both HIV and age on 24-hour GH secretory patterns (Aim 3). Summary: This will be the first study to evaluate 1) an association of IGF-I with the physical function trajectory among older HIV+ adults, 2) the impact of ART initiation on IGF-I among persons with HIV, and 3) the 24-hour GH secretion patterns in older adults with or without HIV infection. Dr. Erlandson's implementation of this mentored research and training proposal "The Impact of HIV and Aging on Physical Function and the Somatopause," will facilitate her development into an independent investigator and leader in the fields of HIV, successful aging, and physical function.