接受含依非韦伦抗逆转录病毒治疗且接受或未接受基于利福平抗结核治疗的华裔HIV感染者的治疗药物监测和药物遗传学研究
Therapeutic drug monitoring and pharmacogenetic study of HIV-infected ethnic Chinese receiving efavirenz-containing antiretroviral therapy with or without rifampicin-based anti-tuberculous therapy.
作者信息
Lee Kuan-Yeh, Lin Shu-Wen, Sun Hsin-Yun, Kuo Ching-Hua, Tsai Mao-Song, Wu Bing-Ru, Tang Sue-Yo, Liu Wen-Chun, Chang Sui-Yuan, Hung Chien-Ching
机构信息
Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan ; Department of Pharmacy, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
出版信息
PLoS One. 2014 Feb 14;9(2):e88497. doi: 10.1371/journal.pone.0088497. eCollection 2014.
OBJECTIVES
Plasma efavirenz concentrations in HIV-infected patients with tuberculosis (TB) may be affected by cytochrome P450 (CYP) 2B6 single-nucleotide polymorphisms and concurrent rifampicin use. We aimed to investigate the effects of CYP2B6 G516T polymorphisms and concomitant rifampicin use on the plasma efavirenz concentrations in HIV-infected Taiwanese.
METHODS
HIV-infected patients with or without TB who had received combination antiretroviral therapy containing efavirenz (600 mg daily) for two weeks or greater were enrolled for determinations of CYP2B6 G516T polymorphism and plasma efavirenz concentrations with the use of polymerase-chain-reaction restriction fragment-length polymorphism and high-performance liquid chromatography, respectively.
RESULTS
From October 2009 to August 2012, 171 HIV-infected patients, including 18 with TB, were enrolled 113 (66.1%) with CYP2B6 G516G, 55 (32.2%) GT, and 3 (1.8%) TT genotype. Patients receiving rifampicin had a significantly lower median plasma efavirenz concentration than the control group (2.16 vs 2.92 mg/L, P = 0.003); however, all patients achieved target plasma concentration (>1 mg/L). Patients with GT or TT genotype had a significantly higher plasma concentration than those with GG genotype (2.50 vs 3.47 mg/L for GT genotype and 8.78 mg/L for TT genotype, P<0.001). Plasma efavirenz concentration >4 mg/L was noted in 38 (22.2%) patients, which was associated with a lower weight (per 10-kg increase, odds ratio, 0.52; 95% confidence interval, 0.33-0.83) and GT or TT genotype (odds ratio, 4.35; 95% confidence interval, 1.97-9.59) in multivariate analysis.
CONCLUSIONS
Despite combination with rifampicin, sufficient plasma efavirenz concentrations can be achieved in HIV-infected Taiwanese with TB who receive efavirenz 600 mg daily. Carriage of CYP2B6 516 GT and TT genotypes and a lower weight are associated with higher plasma efavirenz concentrations.
目的
合并结核病（TB）的HIV感染患者的血浆依非韦伦浓度可能受到细胞色素P450（CYP）2B6单核苷酸多态性及同时使用利福平的影响。我们旨在研究CYP2B6 G516T多态性及同时使用利福平对台湾HIV感染患者血浆依非韦伦浓度的影响。
方法
纳入接受含依非韦伦（每日600 mg）的联合抗逆转录病毒治疗两周或更长时间的合并或未合并TB的HIV感染患者，分别采用聚合酶链反应-限制性片段长度多态性和高效液相色谱法测定CYP2B6 G516T多态性和血浆依非韦伦浓度。
结果
2009年10月至2012年8月，共纳入171例HIV感染患者，其中18例合并TB，113例（66.1%）为CYP2B6 G516G基因型，55例（32.2%）为GT基因型，3例（1.8%）为TT基因型。接受利福平治疗的患者血浆依非韦伦中位浓度显著低于对照组（2.16 vs 2.92 mg/L，P = 0.003）；然而，所有患者均达到目标血浆浓度（>1 mg/L）。GT或TT基因型患者的血浆浓度显著高于GG基因型患者（GT基因型为2.50 vs 3.47 mg/L，TT基因型为8.78 mg/L，P<0.001）。38例（22.2%）患者的血浆依非韦伦浓度>4 mg/L，多因素分析显示这与较低体重（每增加10 kg，比值比为0.52；95%置信区间为0.33 - 0.83）和GT或TT基因型（比值比为4.35；95%置信区间为1.97 - 9.59）相关。
结论
尽管同时使用利福平，但对于每日接受600 mg依非韦伦治疗的合并TB的台湾HIV感染患者，仍可达到足够的血浆依非韦伦浓度。携带CYP2B6 516 GT和TT基因型以及较低体重与较高的血浆依非韦伦浓度相关。
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