Multi-Dimensional Successful Aging Among HIV-Infected Adults

描述(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递增。到2015年，美国将有一半的艾滋病毒感染者年龄超过50岁，这一数字预计还会继续上升。虽然人们对艾滋病毒老龄化的兴趣与日俱增，但关于艾滋病毒成功老龄化的研究却很少。我们将成功老龄化定义为具有生理、认知和心理社会领域的多维结构，其下游结果是自我感知的成功老龄化。这项拟议的研究将是第一次大规模调查，与匹配良好的非艾滋病毒感染对照对象(NC)相比，研究积极的心理因素，如韧性、坚韧、乐观和社会参与，以及基于实验室的生物衰老和艾滋病毒疾病严重程度的系统标记物与艾滋病毒个体成功老龄化的不同领域的关系。研究对象包括120名成年爱滋病病毒感染者和90名年龄在36至65岁的非华裔人士。这些生物标记物将包括：端粒长度、F2-异前列腺素、炎症标记物(高敏C反应蛋白、IL-6、d-二聚体、肿瘤坏死因子-α、CCL2、d-二聚体和sCD14)、胰岛素抵抗和变态负荷，以及艾滋病毒感染者中艾滋病毒疾病严重程度的指标(血浆艾滋病毒病毒负荷、CD4 T细胞计数、艾滋病/非艾滋病)。每个十年(36-45、46-55、56-65)的参与者将使用结构化多队列纵向设计(SMLD)进行评估，每十年均衡招募40名艾滋病毒受试者和30名艾滋病毒受试者。SMLD能够将队列效应与发育(受试者内部)衰老效应分开，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年的跟踪调查，每两年面对面访问一次，以进行详细评估，并在未亲自见到受试者的年份通过后续电话采访和邮寄调查进行评估。我们将研究其纵向轨迹 临床结局指标和积极心理因素，以及衰老和HIV疾病的生物标志物，并与正常对照组进行比较。我们的第一个目标是确定HIV和NC组之间成功衰老的轨迹是否以及如何不同。我们还将在HIV和NC组中确定成功老化轨迹的预测因素。该项目与NIMH战略目标2有关：绘制疾病轨迹图，以确定何时、何地以及如何对HIV感染者进行干预。这项研究的新颖之处在于，它侧重于艾滋病毒成人成功衰老的多维表征和预测因素的识别，以及允许区分队列和发育衰老影响的先进统计方法的使用。我们预计，成功的衰老轨迹将在HIV和NC组之间有所不同，这表明在非HIV感染者中建立的成功老龄化范例不能简单地推广到HIV感染者。在个体水平上了解潜在的可塑性保护因素和风险因素可能会导致开发新的干预措施，旨在增加艾滋病毒携带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.