Bhattacharya Debika, Gupta Amita, Tierney Camlin, Huang Sharon, Peters Marion G, Chipato Tsungai, Martinson Frances, Mohtashemi Neaka, Dula Dingase, George Kathy, Chaktoura Nahida, Klingman Karin L, Gnanashanmugam Devasena, Currier Judith S, Fowler Mary G
University of California, Los Angeles, Los Angeles, California, USA.
Johns Hopkins University, Baltimore, Maryland, USA.
Clin Infect Dis. 2021 Apr 26;72(8):1342-1349. doi: 10.1093/cid/ciaa244.
Severe hepatotoxicity in people with human immunodeficiency virus (HIV) receiving efavirenz (EFV) has been reported. We assessed the incidence and risk factors of hepatotoxicity in women of childbearing age initiating EFV-containing regimens.
In the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, ART-naive pregnant women with HIV and CD4 count ≥ 350 cells/μL and alanine aminotransferase ≤ 2.5 the upper limit of normal were randomized during the antepartum and postpartum periods to antiretroviral therapy (ART) strategies to assess HIV vertical transmission, safety, and maternal disease progression. Hepatotoxicity was defined per the Division of AIDS Toxicity Tables. Cox proportional hazards models were constructed with covariates including participant characteristics, ART regimens, and timing of EFV initiation.
Among 3576 women, 2435 (68%) initiated EFV at a median 121.1 weeks post delivery. After EFV initiation, 2.5% (61/2435) had severe (grade 3 or higher) hepatotoxicity with an incidence of 2.3 (95% confidence interval [CI], 2.0-2.6) per 100 person-years. Events occurred between 1 and 132 weeks postpartum. Of those with severe hepatotoxicity, 8.2% (5/61) were symptomatic, and 3.3% (2/61) of those with severe hepatotoxicity died from EFV-related hepatotoxicity, 1 of whom was symptomatic. The incidence of liver-related mortality was 0.07 (95% CI, .06-.08) per 100 person-years. In multivariable analysis, older age was associated with severe hepatotoxicity (adjusted hazard ratio per 5 years, 1.35 [95% CI, 1.06-1.70]).
Severe hepatotoxicity after EFV initiation occurred in 2.5% of women and liver-related mortality occurred in 3% of those with severe hepatotoxicity. The occurrence of fatal events underscores the need for safer treatments for women of childbearing age.
有报告称，接受依非韦伦（EFV）治疗的人类免疫缺陷病毒（HIV）感染者会出现严重肝毒性。我们评估了开始含EFV治疗方案的育龄妇女肝毒性的发生率及危险因素。
在“促进全球母婴生存”（PROMISE）试验中，未接受过抗逆转录病毒治疗（ART）、HIV阳性、CD4细胞计数≥350个/μL且丙氨酸转氨酶≤正常上限2.5倍的孕妇，在产前和产后阶段被随机分配至不同的抗逆转录病毒治疗（ART）策略组，以评估HIV垂直传播、安全性及母体疾病进展情况。肝毒性根据艾滋病毒性表进行定义。构建Cox比例风险模型，纳入的协变量包括参与者特征、ART方案及EFV开始使用时间。
在3576名女性中，2435名（68%）在产后中位数121.1周时开始使用EFV。开始使用EFV后，2.5%（61/2435）出现严重（3级或更高）肝毒性，发病率为每100人年2.3例（95%置信区间[CI]，2.0 - 2.6）。事件发生在产后1至132周之间。在出现严重肝毒性的患者中，8.2%（5/61）有症状，3.3%（2/61）因EFV相关肝毒性死亡，其中1例有症状。肝脏相关死亡率为每100人年0.07例（95% CI，0.06 - 0.08）。多变量分析显示，年龄较大与严重肝毒性相关（每5岁调整后风险比，1.35 [95% CI，1.06 - 1.70]）。
开始使用EFV后，2.5%的女性出现严重肝毒性，严重肝毒性患者中有3%出现肝脏相关死亡。致命事件的发生凸显了为育龄妇女提供更安全治疗方法的必要性。
