Périard D, Telenti A, Sudre P, Cheseaux J J, Halfon P, Reymond M J, Marcovina S M, Glauser M P, Nicod P, Darioli R, Mooser V
Division of Infectious Diseases, Department of Pediatrics CHUV University Hospital, Lausanne, Switzerland.
Circulation. 1999 Aug 17;100(7):700-5. doi: 10.1161/01.cir.100.7.700.
Administration of protease inhibitors (PIs) to HIV-infected individuals has been associated with hyperlipidemia. In this study, we characterized the lipoprotein profile in subjects receiving ritonavir, indinavir, or nelfinavir, alone or in combination with saquinavir.
Plasma lipoprotein levels were quantified in 93 HIV-infected adults receiving PIs. Comparison was done with pretreatment values and with 28 nonPI-treated HIV-infected subjects. An elevation in plasma cholesterol levels was observed in all PI-treated groups but was more pronounced for ritonavir (2.0+/-0.3 mmol/L [mean+/-SEM], n=46, versus 0.1+/-0.2 mmol/L in nonPI treated group, P<0.001) than for indinavir (0.8+/-0.2 mmol/L, n=26, P=0.03) or nelfinavir (1.2+/-0.2 mmol/L, n=21, P=0.01). Administration of ritonavir, but not indinavir or nelfinavir, was associated with a marked elevation in plasma triglyceride levels (1.83+/-0.46 mmol/L, P=0.002). Plasma HDL-cholesterol levels remained unchanged. Combination of ritonavir or nelfinavir with saquinavir did not further elevate plasma lipid levels. A 48% increase in plasma levels of lipoprotein(a) was detected in PI-treated subjects with pretreatment Lp(a) values >20 mg/dL. Similar changes in plasma lipid levels were observed in 6 children receiving ritonavir.
Administration of PIs to HIV-infected individuals is associated with a marked, compound-specific dyslipidemia. The risk of pancreatitis and premature atherosclerosis due to PI-associated dyslipidemia remains to be established.
对感染人类免疫缺陷病毒（HIV）的个体使用蛋白酶抑制剂（PI）与高脂血症有关。在本研究中，我们对单独使用利托那韦、茚地那韦或奈非那韦，或与沙奎那韦联合使用的受试者的脂蛋白谱进行了特征分析。
对93名接受PI治疗的HIV感染成人的血浆脂蛋白水平进行了定量分析。与治疗前的值以及28名未接受PI治疗的HIV感染受试者进行了比较。在所有接受PI治疗的组中均观察到血浆胆固醇水平升高，但利托那韦组更为明显（2.0±0.3 mmol/L[均值±标准误]，n = 46，未接受PI治疗组为0.1±0.2 mmol/L，P<0.001），高于茚地那韦组（0.8±0.2 mmol/L，n = 26，P = 0.03）或奈非那韦组（1.2±0.2 mmol/L，n = 21，P = 0.01）。使用利托那韦而非茚地那韦或奈非那韦与血浆甘油三酯水平显著升高有关（1.83±0.46 mmol/L，P = 0.002）。血浆高密度脂蛋白胆固醇水平保持不变。利托那韦或奈非那韦与沙奎那韦联合使用并未进一步升高血浆脂质水平。在治疗前脂蛋白(a)值>20 mg/dL的接受PI治疗的受试者中，检测到血浆脂蛋白(a)水平升高了48%。在6名接受利托那韦治疗的儿童中也观察到了类似的血浆脂质水平变化。
对HIV感染个体使用PI与明显的、药物特异性血脂异常有关。PI相关血脂异常导致胰腺炎和过早动脉粥样硬化的风险仍有待确定。
