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

PACTG P1045（版本 10）形态和代谢异常的患病率

• 批准号: 7374978
• 负责人: William Thomas Shearer
• 金额: $ 0.68万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374978
• 关键词: PACTG; P1045; VERSION; 10; PREVALENCE

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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。尽管与高效抗逆转录病毒治疗（HAART）相关的HIV护理取得了不可否认的进展，但现在很明显，许多接受这些治疗方案的患者正在发生潜在的有害代谢作用，包括胰岛素抵抗、血脂异常、骨质减少和骨质疏松症以及高乳酸血症。身体脂肪分布的变化通常被称为脂肪营养不良也有描述。这些变化涉及脂肪积聚（腹部内脏肥胖、颈背部脂肪垫或布法罗驼峰、乳房增大、脂肪过多）和脂肪减少（面部、四肢和臀部脂肪萎缩）。虽然与HIV感染患者的这种并发症组合相关的长期风险尚不清楚，但人们越来越担心这些影响可能会影响由于HAART有效抑制病毒而显著延长预期寿命的患者的长期预后。此外，由于对非常明显的身体变化的关切，对本来可以挽救生命的抗逆转录病毒疗法的坚持受到了不利影响。早期的轶事报道导致蛋白酶抑制剂（PI）直接负责代谢和形态学改变的假设。事实上，在HIV阳性和HIV阴性受试者中的研究中有相当多的证据表明，一些PI可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，代谢变化和脂肪分布异常也发生在接受核苷类似物逆转录酶抑制剂（NRTI）治疗的PI初治患者中。除了类别特异性效应外，有新的证据表明，每类药物在其代谢效应的性质和程度上存在差异。除了暴露于含PI和NRTI的方案外，队列研究中还确定了许多非药物风险因素，如年龄、性别、种族和基线身体组成。潜在的有害代谢效应，包括胰岛素抵抗、血脂异常、骨质减少、骨质疏松症、高乳酸血症和脂肪代谢障碍，与HIV感染儿童中延长生命的HAART相关。迄今为止进行的研究提出了非常广泛的结果，关于患病率和与病情的推定关联，以及ART治疗的组成和持续时间。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糖代谢异常、血脂水平、身体成分、脂肪沉积和分布以及骨密度的患病率：1.在纵向上，受艾滋病毒感染的儿童和青少年接受抗逆转录病毒治疗，而未受艾滋病毒感染的儿童和青少年未受艾滋病毒感染。2.接受含PI方案治疗的纵向HIV感染儿童和青年以及未接受含PI方案治疗的纵向HIV感染儿童和青年。3.根据坦纳分期，在纵向上，艾滋病毒感染儿童和青少年接受抗逆转录病毒治疗，而未感染艾滋病毒的儿童和青少年未感染艾滋病毒。此外，该研究将：1。通过与ATN 021合作，比较接受抗逆转录病毒治疗的艾滋病毒感染女性中垂直和水平方向的糖代谢、血脂水平、身体成分、脂肪沉积和分布以及骨密度异常的患病率。2.探讨高效抗逆转录病毒治疗（HAART）暴露时间和HAART治疗的特定成分与糖代谢、血脂水平、身体成分、脂肪沉积和分布以及骨密度异常患病率的关系。3.探讨药物和非药物因素与正在进行的形态学和代谢参数特异性畸变风险之间的关系，