Atherosclerotic Risk and Response to Exercise Intervention in HIV+ Children

描述(由申请人提供)： 随着高效抗逆转录病毒疗法(HAART)在艾滋病毒感染儿童中的广泛使用，不良代谢异常的患病率和范围都有所增加。有证据表明，感染艾滋病毒的成年人患早发性动脉粥样硬化性心血管疾病的风险增加，并与代谢异常有关。然而，人们对艾滋病毒感染儿童的心血管风险知之甚少。HIV感染者的慢性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。关于HIV感染儿童的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风险因素。我们还提出了一种干预措施，以治疗不利的心血管危险因素(内皮功能障碍、不利的代谢特征)，并改善临床结果，如生活质量。在具体目标1中，我们将前瞻性地招募100名艾滋病毒感染儿童及其100名兄弟姐妹参加一项横断面研究，评估血管炎症途径(炎症、内皮功能障碍、促凝血剂和代谢功能障碍的生物标志物)和血管功能障碍(通过血流介导的血管扩张研究[FMD]和颈动脉内膜中层厚度)，并将水平与身体成分(脂肪再分配)、血脂和胰岛素抵抗(HOMA-IR评分)相关联。在具体目标2中，我们将确定为期12周(每周2次访问)的联合抵抗和有氧运动干预对HIV感染儿童的营养、心血管和临床结果的影响。感染艾滋病毒的儿童(来自目标1)将被平均分为积极运动干预(40)和注意力控制(40)组[目标为每组25人]。这组人将在3个月后接受干预。将在基线、3个月(干预结束时)和6个月(干预结束后3个月)对最大心肌摄氧量、血管内皮功能障碍(上文综述的研究)、身体成分、血脂、胰岛素抵抗、生活质量和依从性进行基线研究。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，并将确定有组织的运动计划是否积极地改变了艾滋病毒感染儿童的这些异常。(摘要结束)

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)