Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
J Antimicrob Chemother. 2010 Mar;65(3):543-7. doi: 10.1093/jac/dkp446. Epub 2009 Dec 23.
Patients with chronic hepatitis C virus (HCV) infection experience antiretroviral-associated liver toxicity more frequently than HIV mono-infected persons. Herein, we report the hepatic safety profile of raltegravir in a relatively large group of HIV/HCV co-infected patients, a population that was poorly represented in the registrational studies.
Prospective, observational study of all antiretroviral-experienced HIV-infected patients who initiated raltegravir from January 2006 to January 2009 at a reference HIV clinic. Clinical data, laboratory parameters and liver stiffness measured at baseline, week 4 and every 3 months thereafter were collected. Chronic hepatitis C was defined as positive serum HCV-RNA. Grade 1-4 hepatotoxicity was defined following the AIDS Clinical Trials Group definition for liver enzyme elevations (LEEs). A control group of patients who initiated protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) was examined similarly.
Data from 218 HIV-infected patients on raltegravir were analysed, 126 HIV mono-infected and 92 HIV/HCV co-infected patients. Any degree of LEEs occurred in 10 (7.9%) HIV mono-infected and 23 (25%) co-infected patients (relative risk 3.1; 95% confidence interval 2.9-3.4; P = 0.002). Severe hepatotoxicity (grade 3-4), however, was only seen in 3 (1.4%) patients, all co-infected with HCV. It occurred at months 1, 15 and 15, respectively. In all three subjects other reasons than raltegravir exposure most likely explained LEEs. Multivariate analysis revealed HCV co-infection as the only independent variable associated with any degree of hepatotoxicity on raltegravir (P = 0.03). Finally, the rate of LEEs in patients on raltegravir was lower than in those who were treated with PIs or NNRTIs.
LEEs are less frequent in patients treated with raltegravir than with other antiretroviral drug classes. However, HIV/HCV co-infected patients treated with raltegravir experienced LEEs more frequently than HIV mono-infected persons. In this series, LEEs in patients treated with raltegravir were uniformly mild and no cases of grade 3-4 hepatotoxicity could be directly attributed to the drug. These results reinforce the overall hepatic safety profile of raltegravir.
慢性丙型肝炎病毒（HCV）感染患者比 HIV 单一感染患者更常经历抗逆转录病毒相关的肝毒性。在此，我们报告了在一组较大的 HIV/HCV 合并感染患者中，raltegravir 的肝安全性概况，该人群在注册研究中代表性不足。
这是一项对 2006 年 1 月至 2009 年 1 月期间在一家参考 HIV 诊所接受过抗逆转录病毒治疗的所有 HIV 感染患者进行的前瞻性、观察性研究。收集基线、第 4 周和此后每 3 个月的临床数据、实验室参数和肝脏硬度值。慢性丙型肝炎的定义为血清 HCV-RNA 阳性。根据艾滋病临床试验组（AIDS Clinical Trials Group）定义的肝酶升高（LEEs）来定义 1-4 级肝毒性。同样检查了接受蛋白酶抑制剂（PI）或非核苷逆转录酶抑制剂（NNRTI）治疗的患者的对照组。
分析了 218 名接受 raltegravir 治疗的 HIV 感染患者的数据，其中 126 名 HIV 单一感染和 92 名 HIV/HCV 合并感染患者。10 名（7.9%）HIV 单一感染和 23 名（25%）合并感染患者出现任何程度的 LEEs（相对风险 3.1；95%置信区间 2.9-3.4；P = 0.002）。然而，仅在 3 名（1.4%）合并 HCV 感染的患者中观察到严重肝毒性（3-4 级）。分别在第 1、15 和 15 个月发生。在所有这三个患者中，与 raltegravir 暴露无关的其他原因很可能解释了 LEEs。多变量分析显示，HCV 合并感染是 raltegravir 治疗相关任何程度肝毒性的唯一独立变量（P = 0.03）。最后，raltegravir 治疗患者的 LEEs发生率低于接受 PI 或 NNRTI 治疗的患者。
与其他抗逆转录病毒药物类别相比，raltegravir 治疗患者的 LEEs 较少发生。然而，接受 raltegravir 治疗的 HIV/HCV 合并感染患者比 HIV 单一感染患者更常发生 LEEs。在本系列中，raltegravir 治疗患者的 LEEs 均为轻度，无 3-4 级肝毒性病例可直接归因于药物。这些结果强化了 raltegravir 的整体肝安全性概况。
