PACTG 1045: PREVALENCE OF MORPHOLOGIC AND METABOLIC ABNORMALITIES IN HIV YOUTH

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、颈部背部脂肪垫或水牛驼背、乳房增大、脂肪瘤)和脂肪减少(面部、四肢和臀部的脂肪萎缩)。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可以诱导耐药性，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。除了特定类别的作用外，有新的证据表明，每一类药物在其代谢作用的性质和大小上都存在差异。除了暴露于PI和NRT方案之外，在队列研究中还确定了一些非药物危险因素，如年龄、性别、种族和基线身体成分。

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 viseral 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 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 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 nucloside 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 matabolic effects. In addition to exposure to both PI- and NRT-containing regimens, a number of non-drug risk factors such as age, gender, race, and baseline body composition have been identified in cohort studies.