PACTG P1045 (VERSION 10) PREVALENCE OF MORPHOLOGIC AND METABOLIC ABNORMALITI

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。尽管与高效抗逆转录病毒治疗（HAART）相关的艾滋病毒护理取得了无可争议的进展，但现在很明显，许多接受这些治疗的患者正在产生潜在的有害代谢影响，包括胰岛素抵抗、血脂异常、骨质减少和骨质疏松以及高乳酸血症。通常被称为脂肪营养不良的身体脂肪分布的变化也被描述过。这些变化包括脂肪积累（腹部内脏肥胖、颈背脂肪垫或水牛驼峰、乳房增大、脂肪增多症）和脂肪减少（面部、四肢和臀区脂肪萎缩）。尽管与HIV感染患者的这种并发症组合相关的长期风险尚不清楚，但越来越多的人担心，这些影响可能会影响由于HAART有效抑制病毒而显着延长预期寿命的患者的长期预后。此外，对非常明显的身体变化的担忧对坚持抗逆转录病毒治疗产生了不利影响。早期的轶事报道导致假设蛋白酶抑制剂（pi）是代谢和形态改变的直接原因。事实上，在HIV阳性和HIV阴性受试者的研究中都有相当多的证据表明，一些pi可以诱导胰岛素抵抗，增加甘油三酯和胆固醇水平。然而，现在清楚的是，在接受核苷类似物逆转录酶抑制剂（NRTIs）治疗的pi初发患者中，代谢变化和脂肪分布异常也会发生。除了类别特异性作用外，越来越多的证据表明，每种药物在其代谢作用的性质和程度上都存在差异。除了暴露于含有PI-和nrti的方案外，许多非药物风险因素，如年龄、性别、种族和基线身体成分，已在队列研究中确定。潜在的有害代谢影响，包括胰岛素抵抗、血脂异常、骨质疏松、骨质疏松、高乳酸血症和脂肪营养不良，与艾滋病毒感染儿童的延长生命的HAART治疗有关。迄今为止进行的研究在患病率和与病情的假定关联以及ART治疗的组成和持续时间方面的发现非常广泛。更大的前瞻性研究需要标准化的定义，人体测量和实验室评估。本研究将比较以下人群中葡萄糖代谢、血脂水平、身体组成、脂肪沉积和分布以及骨密度异常的患病率：1。感染艾滋病毒的儿童和青年接受抗逆转录病毒治疗，未感染艾滋病毒的儿童和青年接受抗逆转录病毒治疗。2. 纵向感染艾滋病毒的儿童和青年接受含pi的治疗方案，纵向感染艾滋病毒的儿童和青年不接受含pi的治疗方案。3. 艾滋病毒感染的儿童和青少年在抗逆转录病毒治疗和艾滋病毒未感染的儿童和青少年根据坦纳阶段。此外，本研究将：1。通过与atn021合作，比较接受抗逆转录病毒治疗的垂直和水平hiv感染女性中糖代谢、血脂水平、身体组成、脂肪沉积和分布以及骨密度异常的患病率。2. 探讨高活性抗逆转录病毒治疗（HAART）的持续时间和HAART治疗的特定成分与糖代谢、血脂水平、身体组成、脂肪沉积和分布以及骨密度异常患病率的关系。3. 目的：探讨药物和非药物因素与糖尿病患者的形态和代谢参数特异性畸变的关系

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite unarguable advances in HIV care associated with highly active antiretroviral therapy (HAART), it is now apparent that many patients on these regimens are developing potentially deleterious metabolic effects, including insulin resistance, dyslipidemia, osteopenia and osteoporosis, and hyperlactatemia. Changes in body fat distribution often referred to as lipodystrophy have also been described. These changes involve both fat accumulation (abdominal visceral obesity, dorsocervical fat pad or buffalo hump, breast enlargement, lipomatosis) and fat loss (lipoatrophy in the face, limbs and gluteal regions). Although the long-term risks associated with this combination of complications in patients with HIV infection are unknown, there is mounting concern that these effects may impact the long-term prognosis in patients whose life expectancies have been significantly extended due to effective viral suppression by HAART. Moreover, adherence to otherwise life-saving antiretroviral therapy has been adversely influenced by the concern about the very obvious physical changes. Early anecdotal reports led to the assumption that protease inhibitors (PIs) were directly responsible for both the metabolic and morphologic alterations . Indeed, there is considerable evidence from studies in both HIV- positive and HIV-negative subjects that some PIs can induce insulin resistance and increase triglyceride and cholesterol levels. However, it is now clear that both metabolic changes and fat distribution abnormalities also occur in PI-naive patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs). In addition to class-specific effects, there is emerging evidence that there are differences with each class of drugs in the nature and magnitude of their metabolic effects. In addition to exposure to both PI- and NRTI-containing regimens, a number of non-drug risk factors such as age, gender, race, and baseline body composition have been identified in cohort studies. Potentially deleterious metabolic effects, including insulin resistance, dyslipidemia, osteopenia, osteoporosis, hyperlactatemia, and lipodystrophy are being associated with life-prolonging HAART in HIV-infected children. Studies conducted to date present a very wide range in findings, with regard to both prevalence and putative associations with the conditions, and composition and duration of ART therapy. Much larger prospective studies are needed with standardized definitions, anthropometric measurements, and laboratory evaluations. This study will compare the prevalence of abnormalities in glucose metabolism, serum lipid levels, body composition, fat deposition and distribution, and bone density in: 1. vertically HIV-infected children and youth on ART and HIV-uninfected children and youth. 2. vertically HIV-infected children and youth who are receiving PI-containing regimens and vertically HIV- infected children and youth who are not receiving PI-containing regimens. 3. vertically HIV-infected children and youth on ART and HIV-uninfected children and youth according to Tanner stage. Additionally, the study will: 1. To compare the prevalence of abnormalities in glucose metabolism, serum lipid levels, body composition, fat deposition and distribution, and bone density in vertically and horizontally HIV-infected females on ART through collaboration with ATN 021. 2. To explore the relationship of duration of exposure to highly active antiretroviral therapy (HAART) and the specific components of HAART therapy to prevalence of abnormalities in glucose metabolism, serum lipid levels, body composition, fat deposition and distribution, and bone density. 3. To explore the relationship between drug and non-drug factors and risk of specific aberrations in the morphologic and metabolic parameters that are being