Barreiro Pablo, Rodríguez-Novoa Sonia, Labarga Pablo, Ruiz Andrés, Jiménez-Nácher Inmaculada, Martín-Carbonero Luz, Gonzalez-Lahoz Juan, Soriano Vincent
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
J Infect Dis. 2007 Apr 1;195(7):973-9. doi: 10.1086/512086. Epub 2007 Feb 20.
Most antiretrovirals are metabolized in the liver, and lower dosing could be advisable in patients with severe liver insufficiency.
Plasma drug levels were measured in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients receiving nevirapine (NVP), efavirenz (EFV), lopinavir/ritonavir (LPV/r), or atazanavir (ATV) with or without ritonavir. Liver fibrosis was measured using elastometry.
A total of 268 coinfected patients with compensated liver disease were analyzed. Mean plasma levels were 6.1 micro g/mL for NVP (35 patients), 2.8 micro g/mL for EFV (46 patients), 5.8 micro g/mL for LPV (56 patients), 0.4 micro g/mL for ATV (58 patients), and 0.7 micro g/mL for ATV/r (73 patients). Overall, drug levels were higher in patients with cirrhosis than in those without cirrhosis for EFV (median, 3.4 vs. 1.9 micro g/mL; P<.01) and NVP (median, 6.6 vs. 5.8 micro g/mL; P=.33). EFV plasma levels above the toxic threshold (>4 micro g/mL) were more frequent in patients with cirrhosis than in those without (31% vs. 3%; P<.001). The same trend was seen for NVP levels >8 micro g/mL (50% vs. 27%; P=.27). By contrast, plasma levels of protease inhibitors (PIs) did not differ significantly between patients with and those without cirrhosis.
Liver clearance of nonnucleoside reverse-transcriptase inhibitors, particularly EFV, is impaired in patients with cirrhosis. No similar effect is seen for PIs. Assessment of liver fibrosis by noninvasive tools may identify HCV/HIV-coinfected patients who might benefit from therapeutic drug monitoring to avoid drug overexposure.
大多数抗逆转录病毒药物在肝脏中代谢，对于严重肝功能不全的患者，降低剂量可能是明智的。
对接受奈韦拉平（NVP）、依非韦伦（EFV）、洛匹那韦/利托那韦（LPV/r）或阿扎那韦（ATV）（加或不加利托那韦）治疗的丙型肝炎病毒（HCV）/人类免疫缺陷病毒（HIV）合并感染患者测定血浆药物水平。使用弹性成像法测量肝纤维化。
共分析了268例代偿性肝病合并感染患者。NVP（35例患者）的平均血浆水平为6.1μg/mL，EFV（46例患者）为2.8μg/mL，LPV（56例患者）为5.8μg/mL，ATV（58例患者）为0.4μg/mL，ATV/r（73例患者）为0.7μg/mL。总体而言，肝硬化患者中EFV（中位数，3.4 vs. 1.9μg/mL；P<0.01）和NVP（中位数，6.6 vs. 5.8μg/mL；P = 0.33）的药物水平高于无肝硬化患者。肝硬化患者中EFV血浆水平高于毒性阈值（>4μg/mL）的情况比无肝硬化患者更常见（31% vs. 3%；P<0.oooo）。NVP水平>8μg/mL时也有相同趋势（50% vs. 27%；P = 0.27）。相比之下，蛋白酶抑制剂（PIs）的血浆水平在有肝硬化和无肝硬化患者之间无显著差异。
肝硬化患者中非核苷类逆转录酶抑制剂，尤其是EFV的肝脏清除受损。PIs未见类似效应。通过非侵入性工具评估肝纤维化可能有助于识别HCV/HIV合并感染患者，这些患者可能受益于治疗药物监测以避免药物过度暴露。
