Multi-Dimensional Successful Aging Among HIV-Infected Adults

艾滋病毒感染者的多维成功老龄化

• 批准号: 8990889
• 负责人: DILIP V. JESTE
• 金额: $ 70.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-09 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8990889
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Affect; Age; Aging; American; Biological Aging; Biological Markers; C-reactive protein; CCL2 gene; CD4 Positive T Lymphocytes; Cell Count; Chronic; Clinical; Cognitive; Cohort Effect; Demographic Factors; Development; Disease; Equilibrium; F2-Isoprostanes; Future; Goals; HIV; Impaired cognition; Individual; Individual Differences; Institutes; Insulin Resistance; Interleukin-6; Intervention; Investigation; Laboratories; Lead; Length; Life; Life Expectancy; Mediator of activation protein; Medical; Methodology; Modeling; National Institute of Mental Health; Older Population; Outcome; Outcome Measure; Participant; Personal Satisfaction; Persons; Physical Function; Physically Handicapped; Plasma; Preventive Intervention; Psychological Factors; Psychosocial Factor; Public Health; Quality of life; Recruitment Activity; Research; Research Design; Risk Factors; Role; Severities; Severity of illness; Spirituality; Structure; Surveys; System; TNF gene; Telephone Interviews; Therapeutic Intervention; Variant; Viral Load result; Visit; age difference; age effect; aged; allostatic load; antiretroviral therapy; base; blood-based biomarker; cognitive function; cohort; design; dimer; follow-up; improved; improved outcome; inflammatory marker; interest; lifestyle factors; longitudinal design; neurobehavioral; novel; optimism; programs; psychosocial; public health relevance; resilience; social; social stress; telomere; working group

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.

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渐延长。到 2015 年，美国一半的艾滋病病毒感染者将超过 50 岁，并且这一数字预计将继续上升。尽管人们对感染艾滋病毒的老龄化问题越来越感兴趣，但仍缺乏关于感染艾滋病毒的成功老龄化的研究。我们将成功老龄化定义为具有身体、认知和社会心理领域的多维结构，下游结果是自我感知的成功老龄化。拟议的研究将是第一个大规模调查，探讨积极的心理因素（例如复原力、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与成功衰老的不同领域之间的关系。 HIV+ 个体与匹配良好的非 HIV 感染者（NC）进行比较。受试者将包括 120 名 HIV+ 成年人和 90 名 36-65 岁的 NC 人。生物标志物包括：端粒长度、F2-异前列腺素、炎症标志物（高敏 C 反应蛋白、IL-6、d-二聚体、TNF-α、CCL2、d-二聚体和 sCD14）、胰岛素抵抗和稳态负荷，以及 HIV+ 个体中 HIV 疾病严重程度的指标（血浆 HIV 病毒载量、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，平衡招募每十年提供 40 名 HIV+ 受试者和 30 名 HIV- 受试者。 sMLD 能够将队列效应与发育（受试者内）衰老效应分开，使我们能够估计 36-65 岁整个年龄范围的衰老轨迹。受试者将被跟踪长达 4 年，每年两次进行面对面访问以进行详细评估，并在未亲自见到受试者的年份通过后续电话访谈和邮件调查进行评估。我们将检查纵向轨迹 临床结果测量和积极的心理因素以及衰老和艾滋病毒疾病的生物标志物，并将其与 NC 受试者进行比较。我们的首要目标是确定 HIV+ 组和 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 群体成功老龄化轨迹的预测因子。该项目与 NIMH 战略目标 #2 相关：绘制疾病轨迹以确定何时、何地以及如何对 HIV+ 个体进行干预。这项研究的新颖之处在于它重点关注艾滋病病毒感染者成功衰老的多维特征和预测因素的识别，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 HIV+ 和 NC 群体之间的成功老龄化轨迹将有所不同，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。了解个人层面上潜在的可塑性保护因素与风险因素可能会导致开发新的干预措施，旨在增加艾滋病毒感染者成功老龄化的可能性。