Chuck Susan K, Penzak Scott R
Department of Pharmacy and Drug Information, Grady Health System-I.D. Program, 341 Ponce de Leon Avenue NE, Atlanta, GA 30308, USA.
Expert Opin Drug Saf. 2002 May;1(1):5-17. doi: 10.1517/14740338.1.1.5.
HIV protease inhibitors decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with serum lipid elevations, which may pose an increased risk of cardiovascular disease and pancreatitis. Treatment of protease inhibitor-related hyperlipidaemia (PIH) is complicated by drug interactions, which significantly increase concentrations of most 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). Although pravastatin and atorvastatin effectively lower cholesterol and triglyceride concentrations in HIV-infected patients, a significant number of patients did not achieve their National Cholesterol Education Program low density lipoprotein concentration goals. Nonetheless, due to the increased risk of rhabdomyolysis with elevated statin concentrations, atorvastatin should be considered a second-line agent. The limited available PIH data supports the fact that pravastatin and atorvastatin are well-tolerated in HIV-infected individuals. More data are needed on the appropriate starting doses, maximum safe doses, role of combination statin-fibrate therapy, documentation of coronary heart disease benefit and incidence of myotoxicity and hepatotoxicity. Pravastatin has an acceptable risk-benefit ratio in PIH, while theoretical toxicity concerns exist with atorvastatin.
HIV蛋白酶抑制剂可降低HIV感染患者的死亡率并改善其生活质量。然而，这些药物与血清脂质升高有关，这可能会增加心血管疾病和胰腺炎的风险。蛋白酶抑制剂相关高脂血症（PIH）的治疗因药物相互作用而变得复杂，这种相互作用会显著增加大多数3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂（他汀类药物）的浓度。尽管普伐他汀和阿托伐他汀能有效降低HIV感染患者的胆固醇和甘油三酯浓度，但仍有相当数量的患者未达到美国国家胆固醇教育计划的低密度脂蛋白浓度目标。尽管如此，由于他汀类药物浓度升高会增加横纹肌溶解的风险，阿托伐他汀应被视为二线药物。现有的有限PIH数据支持以下事实：普伐他汀和阿托伐他汀在HIV感染个体中耐受性良好。关于合适的起始剂量、最大安全剂量、他汀类药物与贝特类药物联合治疗的作用、冠心病获益的记录以及肌毒性和肝毒性的发生率，还需要更多数据。在PIH中，普伐他汀的风险效益比是可以接受的，而阿托伐他汀存在理论上的毒性问题。
