Atherosclerotic Risk and Response to Exercise Intervention in HIV+ Children

HIV儿童的动脉粥样硬化风险和运动干预的反应

• 批准号: 7691244
• 负责人: TRACIE L MILLER
• 金额: $ 38.25万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-25 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7691244
• 关键词: Adult; Adverse effects; Aerobic; Aerobic Exercise; Age; Anti-Retroviral Agents; Atherosclerosis; Attention; Biological Markers; Blood Platelets; Blood Vessels; Body Composition; Body fat; Body mass index; CCL2 gene; Cardiac; Cardiovascular system; Child; Childhood; Chronic; Chronic Disease; Clinical; Coagulants; Cross-Sectional Studies; Data; Developed Countries; Developing Countries; Disease; E-Selectin; Equilibrium; Exercise; Exposure to; Fasting; Fatty acid glycerol esters; Fibrinogen; Functional disorder; Glucose; Goals; HIV; HIV Infections; Habits; Highly Active Antiretroviral Therapy; Home environment; Hyperlipidemia; Immune; Individual; Inflammation; Inflammatory; Insulin; Insulin Resistance; Intercellular adhesion molecule 1; Interleukin-6; Intervention; Lead; Length; Leptin; Leukocytes; Life; Life Style; Lipids; Measures; Medial; Mediating; Metabolic; Metabolic syndrome; Morbidity - disease rate; Myocardial; Nutritional; Obesity; Outcome; Oxygen; Oxygen Consumption; Pathway interactions; Pharmaceutical Preparations; Plasminogen Activator Inhibitor 1; Prevalence; Protease Inhibitor; Quality of life; Randomized Controlled Clinical Trials; Recruitment Activity; Research Design; Resistance; Risk; Risk Factors; Sampling; Serum; Severity of illness; Siblings; Smoke; Structure; Terminology; Thick; Time; Training Programs; Vascular Cell Adhesion Molecule-1; Vasodilation; Viral; Visceral; Visit; Weight; abstracting; adiponectin; base; cardiovascular risk factor; childhood cancer survivor; growth promoting activity; improved; mortality; premature; programs; response; sex; survivorship; uptake; vascular endothelial dysfunction

DESCRIPTION (provided by applicant): With greater use of highly active antiretroviral therapy (HAART) in HIV-infected children, adverse metabolic abnormalities have increased both in prevalence and scope. Evidence suggests that adults with HIV infection are at an increased risk of developing premature atherosclerotic CV disease associated with abnormal metabolic profiles. However, far less is known about CV risk in children with HIV. Ongoing chronic inflammation that results from chronic immune activation in HIV-infected individuals may impair vascular endothelial function and further increase the risk of CV disease. Data regarding metabolic syndrome and vascular endothelial dysfunction in HIV-infected children is limited. Therefore, we are proposing a study to understand the extent of vascular dysfunction and identify potential HIV-specific risk factors. We also propose an intervention to treat adverse CV risk factors (endothelial dysfunction, adverse metabolic profiles) and improve clinical outcomes such as quality of life). In Specific Aim 1, we will prospectively recruit 100 HIV- infected children and 100 of their siblings into a cross-sectional study evaluating vascular inflammatory pathways (biomarkers of inflammation, endothelial dysfunction, pro-coagulants and metabolic dysfunction) and vascular dysfunction (through flow-mediated vasodilation studies [FMD] and carotid intimal medial thickness) and will correlate levels with body composition (fat redistribution), lipids and insulin resistance (HOMA-IR scores). In Specific Aim 2, we will determine the effect of a 12-week (2 visits per week) combined resistance and aerobic exercise intervention on nutritional, CV, and clinical outcomes for HIV-infected children. HIV- infected children (from Aim 1) will be equally divided into an active exercise intervention (40) and attention control (40) groups [goal is 25 per group]. This group will be offered the intervention after 3 months. Baseline studies of maximal myocardial oxygen uptake, vascular endothelial dysfunction (studies reviewed above), body composition, lipids, insulin resistance, quality of life and compliance will be compared at baseline, 3 months (at the end of the intervention), and 6 months (3 months after the intervention is completed). Through this study we will determine the extent of vascular dysfunction and its associations with metabolic parameters and will determine whether a structured exercise program positively changes these abnormalities in HIV-infected children. (End of Abstract)

描述（由申请人提供）： 随着艾滋病毒感染儿童更多地使用高效抗逆转录病毒疗法（HAART），不良代谢异常的患病率和范围均有所增加。有证据表明，感染艾滋病毒的成年人患与代谢异常相关的过早动脉粥样硬化性心血管疾病的风险增加。然而，人们对艾滋病毒感染儿童的心血管风险知之甚少。 HIV 感染者长期免疫激活导致的持续慢性炎症可能会损害血管内皮功能，并进一步增加心血管疾病的风险。有关艾滋病毒感染儿童代谢综合征和血管内皮功能障碍的数据有限。因此，我们提议进行一项研究，以了解血管功能障碍的程度并确定潜在的艾滋病毒特异性危险因素。我们还提出了一种干预措施来治疗不良心血管危险因素（内皮功能障碍、不良代谢特征）并改善临床结果（例如生活质量）。在具体目标 1 中，我们将前瞻性地招募 100 名 HIV 感染儿童及其 100 名兄弟姐妹参与一项横断面研究，评估血管炎症途径（炎症生物标志物、内皮功能障碍、促凝剂和代谢功能障碍）和血管功能障碍（通过血流） -介导的血管舒张研究[FMD]和颈动脉内膜中层厚度）并将水平与身体成分（脂肪重新分布）、脂质和胰岛素抵抗相关联（HOMA-IR 分数）。在具体目标 2 中，我们将确定 12 周（每周 2 次就诊）联合阻力和有氧运动干预对 HIV 感染儿童的营养、心血管和临床结果的影响。 HIV 感染儿童（来自目标 1）将被平均分为主动运动干预组 (40 人) 和注意力控制组 (40 人) [目标是每组 25 人]。该组将在 3 个月后接受干预。将在基线、3个月（干预结束时）和6个月时比较最大心肌摄氧量、血管内皮功能障碍（上述研究）、身体成分、血脂、胰岛素抵抗、生活质量和依从性的基线研究（干预完成后3个月）。 通过这项研究，我们将确定血管功能障碍的程度及其与代谢参数的关系，并将确定结构化的锻炼计划是否能积极改变艾滋病毒感染儿童的这些异常。 （摘要完）