Atherosclerotic Risk and Response to Exercise Intervention in HIV+ Children

描述（由申请人提供）： 随着艾滋病毒感染儿童中高效抗逆转录病毒疗法（HAART）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，HIV感染的成人发生与代谢异常相关的过早动脉粥样硬化性CV疾病的风险增加。然而，对艾滋病毒感染儿童的CV风险知之甚少。HIV感染者慢性免疫激活导致的持续慢性炎症可能损害血管内皮功能，并进一步增加CV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，我们建议进行一项研究，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来治疗不良CV风险因素（内皮功能障碍，不良代谢特征）并改善临床结局，如生活质量。在具体目标1中，我们将前瞻性招募100名HIV感染儿童及其100名兄弟姐妹进行横断面研究，评估血管炎症通路。（炎症，内皮功能障碍，促凝血剂和代谢功能障碍）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相关（脂肪再分布）、脂质和胰岛素抵抗（HOMA-IR评分）。在具体目标2中，我们将确定为期12周（每周2次访视）的抗阻和有氧运动联合干预对HIV感染儿童的营养、CV和临床结局的影响。HIV感染儿童（来自目标1）将被平均分为积极运动干预组（40人）和注意力控制组（40人）[目标是每组25人]。这一组将在3个月后进行干预。将在基线、3个月（干预结束时）和6个月（干预完成后3个月）时比较最大心肌摄氧量、血管内皮功能障碍（上文审查的研究）、身体成分、血脂、胰岛素抵抗、生活质量和依从性的基线研究。 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相关性，并确定结构化的运动计划是否能积极改变HIV感染儿童的这些异常。(End摘要）

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)