Calza Leonardo, Manfredi Roberto, Chiodo Francesco
Department of Clinical and Experimental Medicine, Section of Infectious Diseases, University of Bologna Alma Mater Studiorum, S. Orsola Hospital, Via G. Massarenti 11, Bologna 40138, Italy.
Int J Antimicrob Agents. 2003 Aug;22(2):89-99. doi: 10.1016/s0924-8579(03)00115-8.
A wide range of abnormalities of lipid metabolism have been recently described in HIV-infected patients receiving a protease inhibitor (PI)-based highly active antiretroviral therapy, including hypertriglyceridaemia and hypercholesterolaemia. The increase of plasma lipid concentrations may involve up to 70-80% of HIV-positive subjects treated with a PI-containing regimen and are frequently (but not always) associated with the fat redistribution or the lipodystrophy syndrome. Multiple pathogenetic mechanisms by which antiretroviral agents lead to dyslipidaemia have been hypothesized, but they are still controversial. The potential clinicopathological consequences of HIV-associated hyperlipidaemia are not completely known, but several anecdotal observations report an increased risk of premature coronary artery diseases in young HIV-positive individuals receiving PIs, besides peripheral atherosclerosis and acute pancreatitis. A limited-to-significant improvement of increased triglyceride and cholesterol plasma levels was described in patients who replaced PIs with nevirapine, efavirenz or abacavir, but the risks of long-term toxicity and virological relapse of this treatment switching are not completely defined. A hypolipidaemic diet and regular physical exercise may act favorably on dyslipidaemia, but pharmacological therapy becomes necessary when hyperlipidaemia is severe or persists for a long time. The choice of hypolipidaemic drugs is problematic because of potential pharmacological interactions with antiretroviral compounds and other antimicrobial agents, associated with an increased risk of toxicity and intolerance. Statins are considered the first-line therapy for the PI-related hypercholesterolaemia, while fibrates are the cornerstone of drug therapy when predominant hypertriglyceridaemia is of concern.
最近，在接受基于蛋白酶抑制剂（PI）的高效抗逆转录病毒疗法的HIV感染患者中，已发现多种脂质代谢异常情况，包括高甘油三酯血症和高胆固醇血症。接受含PI方案治疗的HIV阳性患者中，高达70%-80%的人血浆脂质浓度会升高，且这些升高情况常常（但并非总是）与脂肪重新分布或脂肪代谢障碍综合征相关。抗逆转录病毒药物导致血脂异常的多种致病机制已被提出，但仍存在争议。HIV相关高脂血症的潜在临床病理后果尚不完全清楚，但一些个案观察报告称，除了外周动脉粥样硬化和急性胰腺炎外，接受PI治疗的年轻HIV阳性个体患早发性冠状动脉疾病的风险增加。用奈韦拉平、依非韦伦或阿巴卡韦替代PI的患者，其血浆甘油三酯和胆固醇水平升高有一定程度至显著改善，但这种治疗转换的长期毒性风险和病毒学复发风险尚未完全明确。低脂饮食和规律体育锻炼可能对血脂异常有积极作用，但当高脂血症严重或长期持续时，药物治疗就变得必要。由于与抗逆转录病毒化合物和其他抗菌药物存在潜在的药物相互作用，增加了毒性和不耐受风险，因此选择降血脂药物存在问题。他汀类药物被认为是治疗PI相关高胆固醇血症的一线疗法，而当主要关注高甘油三酯血症时，贝特类药物是药物治疗的基石。
