Age related determinants of HAND: A 12 year follow-up of CHARTER participants

HAND 的年龄相关决定因素：对 CHARTER 参与者的 12 年随访

• 批准号: 10371574
• 负责人: ROBERT Kernachan HEATON
• 金额: $ 25.42万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-24 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371574
• 关键词: Adult; Affect; Age; Age-Years; Aging; Baltimore; Biological; Biological Aging; Blood Vessels; Brain; COVID-19; Cerebrovascular Disorders; Clinical; Cognition Disorders; Cognitive; Cognitive deficits; Communities; Cross-Sectional Studies; DNA; Data; Dementia; Disease; Emotional; Encephalitis; Evaluation; Evolution; Future; HIV; HIV antiretroviral; HIV therapy; Immune; Individual; Interview; Investments; Length; Life; Link; Longitudinal Studies; Longitudinal cohort; Measurement; Medical; Memory; Metabolic; Metabolic syndrome; Mitochondrial DNA; Modernization; Mood Disorders; Nerve Degeneration; Neuraxis; Neurocognitive; Organ; Outcome; Participant; Persons; Pharmaceutical Preparations; Pharmacology; Population; RNA; Reporting; Research; Resources; Role; Sampling; Severities; Site; Specimen; Telephone; Time; Viral; Washington; age related; antiretroviral therapy; base; co-infection; cohort; comorbidity; daily functioning; follow-up; functional disability; functional status; insight; interest; medical schools; middle age; neuroAIDS; neurobehavioral; neuroimaging; normal aging; pharmacokinetic model; premature; recruit; research study; substance use; telomere

ABSTRACT Modern antiretroviral therapy (ART) has extended the survival of HIV infected (HIV+) adults into their later years, raising the possibility that age-related organ changes, including neurodegeneration and cerebrovascular disease, might amplify the effects of HIV on the brain. Thus far, data on premature or accelerated central nervous system (CNS) decline have been mostly limited to cross-sectional studies of persons younger than 60 years of age. No longer-term longitudinal studies of HIV+ individuals entering their 7th decade and beyond have been reported. We propose to take advantage of the detailed neuromedical and neurobehavioral information available on 400 HIV+ adults who were initially evaluated as part of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study between 2003 and 2007. Follow-up of this cohort, 200 of whom will be 60 or older, will provide unique 12-year longitudinal data on the combined effects of HIV and ART on CNS decline and resultant functional disability. The major aim will be to build on prior cross-sectional findings comparing HIV+ and HIV- adults to determine if older HIV+ adults (≥ 60 years) have greater CNS decline over 12 years than younger HIV+ adults (< 60 years), while controlling for effects of “normal aging” on neurocognitive function. Adding to the timeliness and relevance of this study: We propose to determine a) how the viral, immune, metabolic/vascular, and pharmacologic correlates of CNS decline differ with age and b) the extent to which indicators of biological aging account for the observed correlations. The project will incorporate multiple state- of-the-art assessments including HIV DNA measurements (an indicator of HIV integration), telomere length and mitochondrial DNA (as indicators of biological aging), and population pharmacokinetic modeling of ART drug concentrations in CSF. CHARTER consists of 6 U.S. academic sites (Johns Hopkins, Baltimore; Icahn School of Medicine at Mt. Sinai, NYC; UC San Diego; UTMB Galveston; Univ. of Washington, Seattle; Washington Univ., St. Louis) that are united by a Coordinating Unit based at UC San Diego. The proposed project will provide the first large scale outcome data on neuroAIDS and aging, and link these to possible mechanisms. In addition, this study will make data and samples available to the scientific community, continuing our strong record of jumpstarting new research and further leveraging the value of the investment in this study.

摘要 现代抗逆转录病毒疗法（ART）延长了HIV感染（HIV+）成人的生存期， 这增加了与年龄相关的器官变化的可能性，包括神经变性和脑血管疾病。 疾病，可能会放大艾滋病毒对大脑的影响。到目前为止，关于过早或加速中心的数据 神经系统（CNS）衰退主要局限于60岁以下人群的横断面研究 岁的没有对进入第七个十年及以后的艾滋病毒阳性个体进行长期纵向研究， 被举报。我们建议利用详细的神经医学和神经行为信息 最初作为CNS HIV抗逆转录病毒治疗的一部分进行评估的400名HIV+成人中可用 2003年至2007年期间的效果研究（CHARTER）。该队列的随访，其中200人将为60岁 或更早的研究，将提供关于HIV和ART对CNS下降的联合作用的独特的12年纵向数据。 导致功能性残疾主要目的是建立在以前的横截面调查结果比较 HIV+和HIV-成人，以确定老年HIV+成人（≥ 60岁）在12年内是否有更大的CNS下降 比年轻的HIV+成人（< 60岁），同时控制“正常老化”对神经认知功能的影响。 增加了这项研究的及时性和相关性：我们建议确定a）病毒，免疫， CNS下降的代谢/血管和药理学相关性随年龄而不同，B） 生物老化指标说明了观察到的相关性。该项目将包括多个国家- 最先进的评估，包括HIV DNA测量（HIV整合的指标），端粒长度 和线粒体DNA（作为生物衰老的指标），以及ART的群体药代动力学建模 CSF中的药物浓度。CHARTER由6个美国学术站点组成（约翰霍普金斯，巴尔的摩;伊坎 医学院在山。纽约州西奈;加州大学圣地亚哥分校; UTMB加尔维斯顿;华盛顿大学，西雅图; 华盛顿大学，圣路易斯），由总部设在加州大学圣地亚哥分校的协调单位统一。拟议 该项目将提供关于神经艾滋病和衰老的第一个大规模结果数据，并将这些数据与可能的 机制等此外，这项研究将向科学界提供数据和样本， 继续保持我们在启动新研究方面的良好记录，并进一步利用投资的价值， 本研究