Chen Dali, Misra Anoop, Garg Abhimanyu
Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
J Clin Endocrinol Metab. 2002 Nov;87(11):4845-56. doi: 10.1210/jc.2002-020794.
Human immunodeficiency virus (HIV) infection is a major global health problem. Recently, combination therapy including HIV-1 protease inhibitors (PIs) has dramatically improved the long-term survival of HIV-infected patients. However, such therapy is associated with a lipodystrophy syndrome characterized by selective loss of sc fat from the face and extremities and, in some patients, accumulation of fat around the neck, dorsocervical region, abdomen, and trunk. Lipodystrophy in HIV-infected patients (LDHIV) is associated with insulin resistance and its metabolic complications such as impaired glucose tolerance, diabetes, hypertriglyceridemia and low serum high density lipoprotein cholesterol levels. PIs appear to be the strongest link to LDHIV; however, fat loss has been reported in some patients taking non-PI antiretroviral drugs. Other factors, such as duration of HIV infection, age, and gender, may also contribute to the risk of development of LDHIV. The molecular basis of LDHIV remains unknown. There is no specific therapy for LDHIV. Avoiding weight gain by reducing energy intake and increasing physical activity may be beneficial in reducing fat accumulation as well as improving metabolic complications. Antihyperglycemic drugs may be used to treat diabetes. Management of dyslipidemia may require lipid-lowering drugs; however, the safety and efficacy of such intervention require further studies. Substitution of PIs with other antiretroviral drugs can mitigate dyslipidemia and glucose intolerance, but whether reversal of lipodystrophy occurs remains unknown. Future research is needed to discover the biochemical and molecular markers of lipodystrophy in HIV patients and develop PIs or other antiretroviral agents that are free of metabolic toxicity.
人类免疫缺陷病毒（HIV）感染是一个重大的全球健康问题。最近，包括HIV-1蛋白酶抑制剂（PIs）在内的联合疗法显著提高了HIV感染患者的长期生存率。然而，这种疗法与一种脂肪代谢障碍综合征相关，其特征是面部和四肢的皮下脂肪选择性减少，在一些患者中，颈部、颈背部、腹部和躯干周围脂肪堆积。HIV感染患者的脂肪代谢障碍（LDHIV）与胰岛素抵抗及其代谢并发症相关，如糖耐量受损、糖尿病、高甘油三酯血症和低血清高密度脂蛋白胆固醇水平。PIs似乎是与LDHIV联系最紧密的因素；然而，在一些服用非PI抗逆转录病毒药物的患者中也有脂肪减少的报道。其他因素，如HIV感染持续时间、年龄和性别，也可能增加LDHIV发生的风险。LDHIV的分子基础尚不清楚。目前尚无针对LDHIV的特异性治疗方法。通过减少能量摄入和增加身体活动来避免体重增加，可能有助于减少脂肪堆积并改善代谢并发症。可使用降糖药物治疗糖尿病。血脂异常的管理可能需要使用降脂药物；然而，这种干预的安全性和有效性需要进一步研究。用其他抗逆转录病毒药物替代PIs可以减轻血脂异常和葡萄糖不耐受，但脂肪代谢障碍是否会逆转仍不清楚。未来需要开展研究，以发现HIV患者脂肪代谢障碍的生化和分子标志物，并开发无代谢毒性的PIs或其他抗逆转录病毒药物。
