Pharmacogenetic & pharmacokinetic biomarker for efavirenz based ARV and rifampicin based anti-TB drug induced liver injury in TB-HIV infected patients.
Pharmacogenetic & pharmacokinetic biomarker for efavirenz based ARV and rifampicin based anti-TB drug induced liver injury in TB-HIV infected patients.
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DOI：
10.1371/journal.pone.0027810
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Aklillu E
中科院分区：
文献类型：
--
作者：
Yimer G;Ueda N;Habtewold A;Amogne W;Suda A;Riedel KD;Burhenne J;Aderaye G;Lindquist L;Makonnen E;Aklillu E
以依非韦伦为基础的抗病毒治疗和抗结核药物性肝损伤（DILI）同时进行的药物遗传变异和依非韦伦药代动力学的意义尚未得到研究。我们进行了一项前瞻性病例对照关联研究，以确定抗结核和抗逆转录病毒药物诱导的肝损伤（DILI）在HIV和结核病（TB）合并感染患者中的发生率、药理学、药代动力学和生化预测指标。新诊断的治疗naïve TB-HIV合并感染患者（n = 353）入组接受以依非韦伦为基础的ART和以利福平为基础的抗结核治疗，并对DILI进行临床和生化评估，最长可达56周。测定血浆依非韦伦和8-羟法韦伦水平，并进行NAT2、CYP2B6、CYP3A5、ABCB1、UGT2B7和SLCO1B1基因分型。使用生存分析和Cox比例风险模型评估DILI的发生率和预测因子的识别。DILI发生率为30.0%，即14.5例/ 1000人周，重症发生率为18.4%，即7.49例/ 1000人周。DILI与女性（p = 0.001）、血浆efavirenz水平升高（p = 0.009）、efavirenz/8-羟favirenz比值（p = 0.036）、基线AST （p = 0.022）、ALT （p = 0.014）、血红蛋白（p = 0.008）、血清白蛋白（p = 0.007）、NAT2慢乙酰化基因型（p = 0.039）和ABCB1 3435TT基因型（p = 0.001）有统计学意义。我们报告了埃塞俄比亚患者中抗结核和抗逆转录病毒DILI的高发病率。患者全身依非韦伦暴露的变异性和NAT2、CYP2B6和ABCB1基因的药理学变异决定了TB-HIV合并感染患者对DILI的易感性。建议在艾滋病毒诊所的早期治疗和/或基因分型实践中密切监测血浆依韦伦水平和肝酶，以便早期识别有DILI风险的患者。
Implication of pharmacogenetic variations and efavirenz pharmacokinetics in concomitant efavirenz based antiviral therapy and anti-tubercular drug induced liver injury (DILI) has not been yet studied. We performed a prospective case-control association study to identify the incidence, pharmacogenetic, pharmacokinetic and biochemical predictors for anti-tubercular and antiretroviral drugs induced liver injury (DILI) in HIV and tuberculosis (TB) co-infected patients. Newly diagnosed treatment naïve TB-HIV co-infected patients (n = 353) were enrolled to receive efavirenz based ART and rifampicin based anti-TB therapy, and assessed clinically and biochemically for DILI up to 56 weeks. Quantification of plasma efavirenz and 8-hydroxyefaviernz levels and genotyping for NAT2, CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 genes were done. The incidence of DILI and identification of predictors was evaluated using survival analysis and the Cox Proportional Hazards Model. The incidence of DILI was 30.0%, or 14.5 per 1000 person-week, and that of severe was 18.4%, or 7.49 per 1000 person-week. A statistically significant association of DILI with being of the female sex (p = 0.001), higher plasma efavirenz level (p = 0.009), efavirenz/8-hydroxyefavirenz ratio (p = 0.036), baseline AST (p = 0.022), ALT (p = 0.014), lower hemoglobin (p = 0.008), and serum albumin (p = 0.007), NAT2 slow-acetylator genotype (p = 0.039) and ABCB1 3435TT genotype (p = 0.001). We report high incidence of anti-tubercular and antiretroviral DILI in Ethiopian patients. Between patient variability in systemic efavirenz exposure and pharmacogenetic variations in NAT2, CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co-infected patients. Close monitoring of plasma efavirenz level and liver enzymes during early therapy and/or genotyping practice in HIV clinics is recommended for early identification of patients at risk of DILI.
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影响因子：
2.6
作者：
di Iulio, Julia;Fayet, Aurelie;Telenti, Amalio
通讯作者：
Telenti, Amalio
影响因子：
13.5
作者：
Huang, YS;Chern, HD;Lee, SD
通讯作者：
Lee, SD
影响因子：
3.4
作者：
Diaz-Molina, Raul;Cornejo-Bravo, Jose M.;Soria-Rodriguez, Carmen G.
通讯作者：
Soria-Rodriguez, Carmen G.
DOI：
10.1097/qai.0b013e318189a7df
发表时间：
2009-03-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Haas DW;Koletar SL;Laughlin L;Kendall MA;Suckow C;Gerber JG;Zolopa AR;Bertz R;Child MJ;Hosey L;Alston-Smith B;Acosta EP;A5213 StudyTeam
通讯作者：
A5213 StudyTeam
影响因子：
3.9
作者：
Faucette, SR;Wang, HB;LeCluyse, EL
通讯作者：
LeCluyse, EL