基因多态性对HIV/AIDS患者依非韦伦血药浓度的影响

Effect of Genetic Polymorphism on the Plasma Concentration of Efavirenz in HIV/AIDS Patients

依非韦伦是抗逆转录病毒治疗中常用的一种非核苷类逆转录酶抑制药,推荐的有效治疗浓度范围为1～4mg·L^(-1)。由于遗传、病理生理、合并用药等因素的影响,依非韦伦个体间血药浓度变异较大,部分使用标准剂量的患者不良反应增加,而另外一些患者却出现病毒学失败。CYP2B6是依非韦伦主要的代谢同工酶,它也是依非韦伦血药浓度个体差异的关键决定因素,其516G>T基因型对药物代谢具有显著影响,常作为调整依非韦伦用量的参考依据。除CYP2B6以外可影响血药浓度的基因还包括CYP2A6、UGT2B7、ABCB1/MDR1等,但不同研究所得结论不尽一致。本文综述影响依非韦伦血药浓度的基因多态性的研究报道,以期能为药物治疗方案调整与个体化用药提供参考。

Efavirenz is a non-nucleoside reverse transcriptaseinhibitor （NNRTI） with narrow therapeutic window （ 1 - 4 mg · L- 1 ）. Several studies have demonstrated that there is considerable intra- and inter-patient variations in plasma efavirenz concentration due to genetic, physiopathologieal factors and combined pharmacotherapy, which may cause virological failure and increase incidence of adverse reactions. The polymorphism of cytochrome P450 （CYP） 2B6, the major enzyme in the efavirenz metabolism pathway, is a key determinant of the significant inter-individual difference in plasma efavirenz concentration. Indeed, the CYP2B6 516 G 〉 T polymorphism appears to be the best predictor of the plasma concentration of efavirenz. Polymorphisms in genes besides CYP2B6 reported to af- fect efavirenz concentrations include those in CYP2A6, UGT2B7 and ABCB1/MDR1 genes, although the results were inconsistent. To provide reference to optimize the use of efavirenz in HIV-1 infected patients, the domestic and foreign literatures that are related to the effect of genetic polymorphism on the plasma concentration of efavirenz were reviewed, analyzed and summarized.