Law W Phillip, Dore Gregory J, Duncombe Chris J, Mahanontharit Apicha, Boyd Mark A, Ruxrungtham Kiat, Lange Joep M A, Phanuphak Praphan, Cooper David A
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.
AIDS. 2003 Oct 17;17(15):2191-9. doi: 10.1097/00002030-200310170-00007.
To examine rates and predictors of severe hepatotoxicity with combination antiretroviral therapy in a developing country setting: the eight HIV-NAT randomized controlled trials in Thailand.
All patients (n = 692) received at least two nucleoside reverse transcriptase inhibitors; 215 also received a non-nucleoside reverse transcriptase inhibitor (NNRTI) and 135 also received a protease inhibitor. Severe hepatotoxicity was defined as an increase in alanine aminotransferase (ALT) level to five times the upper limit of normal and an increase of at least 100 U/l from baseline. Liver function tests were available at baseline and weeks 4, 8, 12, 24, 36 and 48. Hepatitis B virus (HBV) and hepatitis C virus (HCV) testing was performed on stored serum.
Mean age was 32.3 years; 52% were male, 11% had Centers for Disease Control and Prevention category C HIV disease at baseline, and 22% had received prior antiretroviral therapy. Prevalence of HBV, HCV and HBV/HCV coinfection was 8.7%, 7.2%, and 0.4%, respectively. Incidence of severe hepatotoxicity was 6.1/100 person-years [95% confidence interval (CI), 4.3-8.3/100]. In multivariate analysis, predictors of severe hepatotoxicity were HBV or HCV coinfection, and NNRTI-containing therapy. Incidence of severe hepatotoxicity was particularly high among patients receiving nevaripine (18.5/100 person-years; 95% CI, 11.6-27.8) and nevirapine/efavirenz (44.4/100 person-years; 95% CI, 12.1-113.7).
Incidence and risk factors for severe hepatotoxicity appear similar among these Thai patients to those in other racial groups. Development of standardized antiretroviral therapy regimens for developing country settings should consider potential toxicity and capabilities for monitoring of toxicity.
在发展中国家背景下，研究联合抗逆转录病毒疗法导致严重肝毒性的发生率及预测因素：泰国的八项HIV-NAT随机对照试验。
所有患者（n = 692）至少接受两种核苷类逆转录酶抑制剂；215例还接受了非核苷类逆转录酶抑制剂（NNRTI），135例还接受了蛋白酶抑制剂。严重肝毒性定义为丙氨酸氨基转移酶（ALT）水平升高至正常上限的五倍，且较基线水平至少升高100 U/l。在基线以及第4、8、12、24、36和48周进行肝功能检查。对储存的血清进行乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）检测。
平均年龄为32.3岁；52%为男性，11%在基线时患有美国疾病控制与预防中心C类HIV疾病，22%曾接受过抗逆转录病毒治疗。HBV、HCV及HBV/HCV合并感染的患病率分别为8.7%、7.2%和0.4%。严重肝毒性的发生率为6.1/100人年[95%置信区间（CI），4.3 - 8.3/100]。在多变量分析中，严重肝毒性的预测因素为HBV或HCV合并感染以及含NNRTI的治疗方案。接受奈韦拉平治疗的患者中严重肝毒性的发生率特别高（18.5/100人年；95%CI，11.6 - 27.8），接受奈韦拉平/依非韦伦治疗的患者中严重肝毒性的发生率为44.4/100人年（95%CI，12.1 - 113.7）。
这些泰国患者中严重肝毒性的发生率和危险因素与其他种族群体相似。为发展中国家制定标准化抗逆转录病毒治疗方案时应考虑潜在毒性及毒性监测能力。
