Multi-Dimensional Successful Aging Among HIV-Infected Adults

描述（由申请人提供）：接受抗逆转录病毒治疗（ART）的成年人的预期寿命一直在逐步增加。到2015年，美国一半的艾滋病毒阳性者将超过50岁，预计这一数字将继续上升。虽然人们对艾滋病毒老化越来越感兴趣，但缺乏关于艾滋病毒成功老化的研究。我们将成功老龄化定义为一个多维结构，包括身体、认知和心理社会领域，下游结果是自我感知的成功老龄化。拟议的研究将是第一次大规模调查，检查积极的心理因素，如弹性，坚韧，乐观和社会参与沿着与基于实验室的生物衰老和HIV疾病严重程度的系统性标志物的关系，与匹配良好的非HIV感染的比较受试者（NC）相比，HIV+个体成功衰老的不同领域。受试者将包括120名HIV阳性成人和90名年龄在36-65岁之间的NC。生物标志物将包括：端粒长度、F2-异前列腺素、炎性标志物（高敏C反应蛋白、IL-6、d-二聚体、TNF-α、CCL 2、d-二聚体和sCD 14）、胰岛素抵抗和非稳态负荷，以及HIV+个体中的HIV疾病严重性指标（血浆HIV病毒负荷、CD 4 + T细胞计数、AIDS/非AIDS）。将使用结构化多队列纵向设计（sMLD）评价每个十年（36-45、46-55、56-65）的受试者，平衡招募，每十年提供40例HIV+和30例HIV-受试者。sMLD能够将队列效应与发育（受试者内）衰老效应分离，使我们能够估计36-65岁整个年龄范围内的衰老轨迹。将对受试者进行长达4年的随访，每两年进行一次面对面访视以进行详细评估，并在未进行面对面访视的年份通过随访电话访谈和邮件调查进行评价。我们将研究 临床结果测量和积极的心理因素以及衰老和HIV疾病的生物标志物，并将其与NC受试者进行比较。我们的第一个目标是确定艾滋病毒+和NC组之间成功衰老的轨迹是否以及如何不同。我们还将确定HIV+和NC组中成功衰老轨迹的预测因素。该项目与NIMH战略目标#2有关：绘制疾病轨迹，以确定何时，何地以及如何干预艾滋病毒阳性个体。这项研究的新颖之处在于它专注于HIV+成人成功衰老的预测因素的多维表征和识别，以及使用先进的统计方法来区分队列和发育衰老效应。我们预计，成功的老化轨迹将不同的HIV+和NC组之间建立在非HIV感染者的成功的衰老模式不能简单地推广到HIV感染者。在个人层面上了解潜在的可塑性保护因素与风险因素可能会导致制定新的干预措施，旨在增加艾滋病毒感染者成功老龄化的可能性。

DESCRIPTION (provided by applicant): The life expectancy of adults receiving antiretroviral therapy (ART) has been increasing progressively. By 2015 one-half of HIV+ people in the U.S. will be over age 50, and this number is expected to continue to rise. While there has been a growing interest in aging with HIV, there is a dearth of research on successful aging with HIV. We define successful aging as a multi-dimensional construct with physical, cognitive, and psychosocial domains, with the downstream outcome being self-perceived successful aging. The proposed study will be the first large-scale investigation examining the relationship of positive psychological factors such as resilience, hardiness, optimism, and social engagement along with laboratory-based systemic markers of biological aging and HIV disease severity to the different domains of successful aging in HIV+ individuals as compared to well- matched Non-HIV-infected Comparison subjects (NCs). Subjects will include 120 HIV+ adults and 90 NCs aged 36-65 years. The biomarkers will include: telomere length, F2-isoprostanes, inflammatory markers (high- sensitivity C-reactive protein, IL-6, d-dimer, TNF-alpha, CCL2, d-dimer and sCD14), insulin resistance, and allostatic load, and, among HIV+ individuals, indicators of HIV disease severity (plasma HIV viral load, CD4+ T-cell count, AIDS/nonAIDS). Participants in each decade (36-45, 46-55, 56-65) will be evaluated using a structured Multi-cohort Longitudinal Design (sMLD), with balanced recruitment providing 40 HIV+ and 30 HIV- subjects per decade. The sMLD enables separation of cohort effects from developmental (within-subject) aging effects, allowing us to estimate aging trajectories across the entire age range of 36-65 years. Subjects will be followed for up to 4 years, with in-person bi-annual visits for detailed assessments, and evaluated with follow- up telephone interviews and mail surveys in the years in which they are not seen in person. We will examine the longitudinal trajectories of clinical outcome measures and positive psychological factors as well as biomarkers of aging and HIV disease, and compare them to those in NC subjects. Our first aim is to determine whether and how trajectories of successful aging differ between HIV+ and NC groups. We will also identify predictors of successful aging trajectories in HIV+ and NC groups. This project is related to NIMH Strategic Objective #2: charting illness trajectories to determine when, where, and how to intervene with HIV+ individuals. This study is novel in its focus on multi-dimensional characterization and recognition of predictors of successful aging in HIV+ adults as well as the use of advanced statistical methodology that allows for the distinction of cohort and developmental aging effects. We anticipate that successful aging trajectories will differ between HIV+ and NC groups suggesting that successful aging paradigms established in non-HIV-infected cannot be simply be generalized to HIV-infected persons. Understanding potentially malleable protective versus risk factors at an individual level may lead to development of new interventions aimed at increasing the likelihood of successful aging among people living with HIV.