Brown Todd T
Division of Endocrinology and Metabolism, Johns Hopkins University, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA.
J Clin Endocrinol Metab. 2008 Aug;93(8):2937-45. doi: 10.1210/jc.2008-1019.
Subcutaneous atrophy and central fat accumulation are common among HIV-infected patients receiving highly active antiretroviral therapy, and may be accompanied by dyslipidemia and insulin resistance. These fat changes, although commonly referred to together as lipodystrophy, are best considered as separate disorders, with distinct pathogeneses and treatment approaches. These morphological and metabolic abnormalities first appeared after introduction of protease inhibitors more than 10 yr ago, but research has demonstrated that their pathogenesis is multifactorial, with contributions from other antiretroviral medications, patient-related factors, and HIV itself. Switching to a less toxic highly active antiretroviral therapy regimen has shown partial effectiveness for the management of fat atrophy and lipid abnormalities. Lifestyle modification or surgical approaches are the treatment of choice for lipohypertrophy, although novel therapies targeting the GH axis show promise. HIV-related dyslipidemia may be difficult to treat, and can be complicated by drug-drug interactions between some lipid-lowering medications and antiretroviral medications. Treatment of diabetes in HIV-infected patients should generally follow established guidelines, but thiazolidinediones, rather than metformin, may be considered first-line treatment in a patient with lipoatrophy, given their potential to increase sc fat. The contribution of body fat changes and metabolic abnormalities to cardiovascular risk and the changing risk profiles of newer antiretroviral regimens are under intense investigation.
皮下脂肪萎缩和中心性脂肪堆积在接受高效抗逆转录病毒治疗的HIV感染患者中很常见,并且可能伴有血脂异常和胰岛素抵抗。这些脂肪变化虽然通常统称为脂肪代谢障碍,但最好被视为单独的病症,具有不同的发病机制和治疗方法。这些形态和代谢异常在10多年前蛋白酶抑制剂引入后首次出现,但研究表明其发病机制是多因素的,其他抗逆转录病毒药物、患者相关因素和HIV本身都有影响。改用毒性较小的高效抗逆转录病毒治疗方案已显示出对脂肪萎缩和脂质异常管理的部分有效性。生活方式改变或手术方法是脂肪增多症的治疗选择,尽管针对生长激素轴的新型疗法显示出前景。HIV相关的血脂异常可能难以治疗,并且可能因一些降脂药物和抗逆转录病毒药物之间的药物相互作用而变得复杂。HIV感染患者的糖尿病治疗一般应遵循既定指南,但鉴于噻唑烷二酮类药物有增加皮下脂肪的潜力,对于有脂肪萎缩的患者,可考虑将其作为一线治疗药物,而非二甲双胍。身体脂肪变化和代谢异常对心血管风险的影响以及新型抗逆转录病毒治疗方案不断变化的风险特征正在深入研究中。