Hepatotoxicity in an African antiretroviral therapy cohort: the effect of tuberculosis and hepatitis B
Hepatotoxicity in an African antiretroviral therapy cohort: the effect of tuberculosis and hepatitis B
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DOI：
10.1097/qad.0b013e32814e6b08
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发表时间：
2007-06-19
期刊：
影响因子：
3.8
通讯作者：
Grant, Alison D.
中科院分区：
文献类型：
--
作者：
Hoffmann, Christopher J.;Charalambous, Salome;Grant, Alison D.
目的：肝毒性是抗逆转录病毒治疗（ART）的重要并发症。我们评估的发病率和危险因素之间的艾滋病毒感染的个体在ART在南非的肝毒性。设计：我们进行了一项回顾性队列研究，在工作场所的艾滋病护理计划在南非，使用一线方案的依法韦仑，齐多夫定，拉米夫定，并提供常规的临床和实验室monitoring.Methods：我们包括受试者的基线和后续丙氨酸转氨酶和天冬氨酸转氨酶测试。在ART治疗的前12个月内发现了严重的肝毒性病例。从临床记录、数据库查询和血清学检测中确定了潜在的风险因素，包括合并用药、结核病、B型和C型肝炎。使用考克斯比例风险modeling.Results：868例受试者（94%男性，中位年龄41岁），中位最低CD 4细胞计数为136/μ l，25%接受伴随结核病治疗ART期间，和17%的随机选择的子集是阳性的肝炎B表面抗原（HBsAg）。我们确定了每100人-年7.7次严重肝毒性发作。结核病治疗使风险增加8.5倍，HBsAg阳性增加3.0倍，CD 4细胞计数最低值< 100/mu l增加1.9倍。重要的是，部分患者严重肝毒性的ART（4.6%）是相似的分数与肝酶升高> 5倍正常上限开始ART（4%）之前的分数：在这个非洲ART队列，我们发现了一个低发病率和最低的发病率由于肝毒性。H13 sAg和伴随的结核病治疗显着增加了肝毒性的风险。(c)2007年利平科特威廉姆斯&威尔金斯。
Objective: Hepatotoxicity is a significant complication of antiretroviral therapy (ART). We assessed the incidence of and risk factors for hepatotoxicity among HIV-infected individuals on ART in South Africa.Design: We conducted a retrospective cohort study in a workplace HIV care program in South Africa which uses a first-line regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical and laboratory monitoring.Methods: We included subjects with baseline and follow-up alanine transaminase and aspartate aminotransferase tests. Severe hepatotoxicity cases were identified during the first 12 months of ART. Potential risk factors, including concomitant medication use, tuberculosis, and hepatitis B and C, were determined from clinical records, database queries, and serological testing. Associations with hepatotoxicity were investigated using Cox proportional hazards modeling.Results: Of the 868 subjects (94% male, median age 41 years), the median nadir CD4 cell count was 136/mu l, 25% received concomitant tuberculosis treatment during ART, and 17% of a randomly selected subset were positive for hepatitis B surface antigen (HBsAg). We identified 7.7 episodes of severe hepatotoxicity per 100 person-years. Tuberculosis treatment increased risk 8.5 fold, positive HBsAg 3.0 fold, and nadir CD4 cells count < 100/mu l 1.9 fold. Importantly, the fraction of patients with severe hepatotoxicity on ART (4.6%) was similar to the fraction with liver enzyme elevations > 5 times the upper limit of normal before starting ART (4%).Conclusions: In this African ART cohort, we found a low incidence of and minimal morbidity due to hepatotoxicity. H13sAg and concomitant tuberculosis therapy significantly increased the risk of hepatotoxicity.(c) 2007 Lippincott Williams & Wilkins.