Hammond Emma, Nolan David
Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, 6000, Western Australia.
Curr Opin HIV AIDS. 2007 Jul;2(4):274-81. doi: 10.1097/COH.0b013e3281c10df7.
Adipose tissue pathology plays a central role in lipodystrophy. This review discusses the mechanisms by which adipose tissue responses to specific antiretroviral therapy determine clinical outcomes, and key recent data are examined that can inform the successful avoidance or management of such toxicities.
Changes in body composition and hyperlipidaemia that occur with the use of certain thymidine analogues and protease inhibitors are accompanied by profound alterations in adipose tissue. Drug toxicity in adipocytes affects the homeostatic regulation of adipocytokines secreted from adipose tissue that mediate proinflammatory and metabolic effects, both locally and in peripheral tissue. The inflammatory component of adipose pathology may also explain slow gains in fat after switching from toxic therapies.
Lipodystrophy can be avoided by selecting therapies with benign effects on adipose tissue. Switching from certain HIV protease inhibitors may normalize the metabolic profile fairly rapidly. For individuals living with an ongoing burden of lipoatrophy, however, reversal of pathology appears slow, and the systemic implications of adipose pathology per se as a risk factor for cardiovascular disease should be considered. Further investigation of adipose pathology for disease in the HIV community is warranted, with the potential for explorations in therapeutic intervention.
脂肪组织病理学在脂肪营养不良中起核心作用。本综述讨论脂肪组织对特定抗逆转录病毒疗法的反应决定临床结果的机制，并审视了近期的关键数据，这些数据可为成功避免或管理此类毒性提供依据。
使用某些胸苷类似物和蛋白酶抑制剂时出现的身体成分变化和高脂血症伴随着脂肪组织的深刻改变。脂肪细胞中的药物毒性影响脂肪组织分泌的脂肪细胞因子的稳态调节，这些因子在局部和外周组织中介导促炎和代谢作用。脂肪病理学的炎症成分也可能解释从毒性疗法转换后脂肪增加缓慢的原因。
通过选择对脂肪组织有良性影响的疗法可以避免脂肪营养不良。从某些HIV蛋白酶抑制剂转换治疗可能会相当迅速地使代谢状况恢复正常。然而，对于持续存在脂肪萎缩负担的个体，病理逆转似乎缓慢，应考虑脂肪病理学本身作为心血管疾病危险因素的全身影响。有必要对HIV群体中的脂肪病理学疾病进行进一步研究，并有可能探索治疗干预措施。
