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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。尽管与高效抗逆转录病毒疗法(HAART)相关的艾滋病毒治疗取得了无可争议的进步，但现在很明显，许多服用这些方案的患者正在出现潜在的有害代谢效应，包括胰岛素抵抗、血脂异常、骨量减少和骨质疏松，以及高乳酸血症。体脂分布的变化，通常被称为脂肪营养不良，也已被描述。这些变化包括脂肪积累(腹部内脏肥胖症、颈部背部脂肪垫或水牛驼峰、乳房增大、脂肪肿大)和脂肪减少(面部、四肢和臀部脂肪萎缩)。尽管与艾滋病毒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患者的长期预后，这些患者的预期寿命由于HAART的有效病毒抑制而显著延长。此外，由于对非常明显的身体变化的担忧，坚持接受原本可以挽救生命的抗逆转录病毒治疗受到了不利影响。早期的轶事报道导致了一种假设，即蛋白水解酶抑制剂(PI)是代谢和形态改变的直接原因。事实上，从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，并增加甘油三酯和胆固醇水平。然而，现在清楚的是，接受核苷类似物逆转录酶抑制剂(NRTI)治疗的PI初治患者也会发生代谢变化和脂肪分布异常。除了特定类别的影响外，有新的证据表明，每一类药物在其代谢影响的性质和大小上都存在差异。除了接触含有PI和NRTI的方案外，在队列研究中还确定了一些非药物风险因素，如年龄、性别、种族和基线身体成分。潜在的有害代谢影响，包括胰岛素抵抗、血脂异常、骨量减少、骨质疏松症、高乳酸血症和脂肪营养不良，与延长HIV感染儿童的HAART有关。到目前为止进行的研究表明，关于ART治疗的流行率和假定与条件、组成和持续时间的关联，研究结果非常广泛。需要更大规模的前瞻性研究，包括标准化定义、人体测量和实验室评估。本研究将比较以下人群在糖代谢、血脂水平、体成分、脂肪沉积和分布、骨密度等方面的异常患病率：1.垂直感染HIV的儿童和青少年对ART和未感染HIV的儿童和青少年的影响。2.接受含PI方案的垂直感染艾滋病毒的儿童和青年和未接受含PI方案的垂直感染艾滋病毒的儿童和青年。3.根据Tanner Stage，在抗逆转录病毒疗法上垂直感染艾滋病毒的儿童和青年和未感染艾滋病毒的儿童和青年。此外，这项研究还将：1.通过与ATN 021合作，比较接受抗逆转录病毒治疗的垂直和水平感染艾滋病毒的女性在葡萄糖代谢、血脂水平、身体成分、脂肪沉积和分布以及骨密度方面的异常发生率。2.探讨接受高效抗逆转录病毒治疗(HAART)的时间和HAART治疗的特定成分与糖代谢异常、血脂水平、体成分、脂肪沉积和分布以及骨密度异常的关系。3.探讨药物和非药物因素与特定异常风险之间的关系。

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