McKoy June M, Bennett Charles L, Scheetz Marc H, Differding Virginia, Chandler Kevin L, Scarsi Kimberly K, Yarnold Paul R, Sutton Sarah, Palella Frank, Johnson Stuart, Obadina Eniola, Raisch Dennis W, Parada Jorge P
Department of Medicine, Northwestern University Feinberg School of Medicine, and Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois 60611, USA.
Drug Saf. 2009;32(2):147-58. doi: 10.2165/00002018-200932020-00007.
The antiretroviral nevirapine can cause severe hepatotoxicity when used 'off-label' for preventing mother-to-child HIV transmission (PMTCT), newborn post-exposure prophylaxis and for pre- and post-exposure prophylaxis among non-HIV-infected individuals. We describe the incidence of hepatotoxicity with short- versus long-course nevirapine-containing regimens in these groups.
We reviewed hepatotoxicity cases among non-HIV-infected individuals and HIV-infected pregnant women and their offspring receiving short- (<or=4 days) versus long-course (>or=5 days) nevirapine prophylaxis. Sources included adverse event reports from pharmaceutical manufacturers and the US FDA, reports from peer-reviewed journals/scientific meetings and the Research on Adverse Drug events And Reports (RADAR) project. Hepatotoxicity was scored using the AIDS Clinical Trial Group criteria.
Toxicity data for 8216 patients treated with nevirapine-containing regimens were reviewed. Among 402 non-HIV-infected individuals receiving short- (n=251) or long-course (n=151) nevirapine, rates of grade 1-2 hepatotoxicity were 1.99% versus 5.30%, respectively, and rates of grade 3-4 hepatotoxicity were 0.00% versus 13.25%, respectively (p<0.001 for both comparisons). Among 4740 HIV-infected pregnant women receiving short- (n=3031) versus long-course (n=1709) nevirapine, rates of grade 1-2 hepatotoxicity were 0.62% and 7.04%, respectively, and rates of grade 3-4 hepatotoxicity were 0.23% versus 4.39%, respectively (p<0.001 for both comparisons). The rates of grade 3-4 hepatotoxicity among 3074 neonates of nevirapine-exposed HIV-infected pregnant women were 0.8% for those receiving short-course (n=2801) versus 1.1% for those receiving long-course (n=273) therapy (p<0.72).
Therapy duration appears to significantly predict nevirapine hepatotoxicity. Short-course nevirapine for HIV prophylaxis is associated with fewer hepatotoxic reactions for non-HIV-infected individuals or pregnant HIV-infected women and their offspring, but administration of prophylactic nevirapine for >or=2 weeks appears to be associated with high rates of hepatotoxicity among non-HIV-infected individuals and HIV-infected pregnant mothers. When full highly active antiretroviral therapy (HAART) regimens are not available, single-dose nevirapine plus short-course nucleoside reverse transcriptase inhibitors to decrease the development of HIV viral resistance is an essential therapeutic option for PMTCT and these data support the safety of single-dose nevirapine in this setting.
抗逆转录病毒药物奈韦拉平在用于预防母婴传播艾滋病（PMTCT）、新生儿暴露后预防以及非艾滋病病毒（HIV）感染个体的暴露前和暴露后预防时，若使用“非标准用法”可导致严重肝毒性。我们描述了在这些人群中，含奈韦拉平的短疗程与长疗程方案所致肝毒性的发生率。
我们回顾了非HIV感染个体以及接受短疗程（≤4天）与长疗程（≥5天）奈韦拉平预防的HIV感染孕妇及其后代中的肝毒性病例。资料来源包括制药商和美国食品药品监督管理局（FDA）的不良事件报告、同行评审期刊/科学会议的报告以及药物不良事件与报告研究（RADAR）项目。使用艾滋病临床试验组标准对肝毒性进行评分。
对接受含奈韦拉平方案治疗的8216例患者的毒性数据进行了回顾。在402例接受短疗程（n = 251）或长疗程（n = 151）奈韦拉平的非HIV感染个体中，1 - 2级肝毒性发生率分别为1.99%和5.30%，3 - 4级肝毒性发生率分别为0.00%和13.25%（两项比较p均<0.001）。在4740例接受短疗程（n = 3031）与长疗程（n = 1709）奈韦拉平的HIV感染孕妇中，1 - 2级肝毒性发生率分别为0.62%和7.04%，3 - 4级肝毒性发生率分别为0.23%和4.39%（两项比较p均<0.001）。在3074例暴露于奈韦拉平的HIV感染孕妇的新生儿中，接受短疗程（n = 2801）治疗的3 - 4级肝毒性发生率为0.8%，接受长疗程（n = 273）治疗的为1.1%（p<0.72）。
治疗持续时间似乎是奈韦拉平肝毒性的重要预测因素。对于非HIV感染个体或HIV感染孕妇及其后代，用于HIV预防的短疗程奈韦拉平所致肝毒性反应较少，但在非HIV感染个体和HIV感染孕妇中，预防性使用奈韦拉平≥2周似乎与高肝毒性发生率相关。当无法获得完整的高效抗逆转录病毒治疗（HAART）方案时，单剂量奈韦拉平加短疗程核苷类逆转录酶抑制剂以降低HIV病毒耐药性的发生，是PMTCT的重要治疗选择，且这些数据支持了单剂量奈韦拉平在此情况下的安全性。
