利福平及基因多态性对中国HIV合并结核病患者依非韦伦血药浓度的影响

Effects of rifampicin, and polymorphisms on efavirenz plasma concentration in Chinese patients living with HIV and tuberculosis.

作者信息

Zhang Li, Meng Xianmin, Dong Ping, Qi Tangkai, Liu Li, Wang Bin

机构信息

Department of Pharmacy, 159397Huashan Hospital Fudan University, Shanghai, People's Republic of China.

Department of Pharmacy, 34748Shanghai Public Health Clinical Center, Shanghai, People's Republic of China.

出版信息

Int J STD AIDS. 2023 Jan;34(1):37-47. doi: 10.1177/09564624221134137. Epub 2022 Nov 10.

DOI:10.1177/09564624221134137

PMID:36356965

Abstract

BACKGROUND

Tuberculosis (TB) is the leading opportunistic infection of people living with human immunodeficiency virus (HIV; PLWH). Cytochrome P450 (CYP) 2B6 and ATP-binding cassette sub-family B member 1 () are involved in the metabolism and transportation of efavirenz. The study was aimed to investigate the effects of rifampicin, and polymorphisms on efavirenz exposure in Chinese PLWH co-infected with TB.

METHOD

PLWH were screened according to inclusion and exclusion criteria and divided into HIV group and HIV/TB group. Efavirenz plasma concentration (C) was determined, dose-adjusted concentration (C/D) was calculated, and genotypes of 516G>T, 785A>G, and 2677G>T, 3435C>T were analyzed.

RESULTS

252 PLWH were enrolled, including 75 co-infected with TB and concomitant with rifampicin. Efavirenz C and C/D were both higher in HIV group (1.94 μg/mL, 0.2007 (μg/ml)/(mg/kg/d)) compared with HIV/TB group (1.52 μg/mL, 0.1557 (μg/ml)/(mg/kg/d)) ( = .001). Efavirenz C/D was significantly higher in patients with variant genotypes of 516G>T and 785A>G (<.001), and was significantly lower in HIV/TB group compared with HIV group among patients with 516 GG, TT, and 785 AA, AG genotypes ( < .05).

CONCLUSION

Efavirenz exposure is reduced by co-administration with rifampicin, and related to genetic polymorphisms of

摘要

背景

结核病（TB）是人类免疫缺陷病毒（HIV；HIV感染者）感染者中主要的机会性感染。细胞色素P450（CYP）2B6和ATP结合盒亚家族B成员1（）参与依非韦伦的代谢和转运。本研究旨在探讨利福平、和多态性对合并感染TB的中国HIV感染者中依非韦伦暴露的影响。

方法

根据纳入和排除标准对HIV感染者进行筛选，分为HIV组和HIV/TB组。测定依非韦伦血浆浓度（C），计算剂量调整浓度（C/D），并分析516G>T、785A>G以及2677G>T、3435C>T的基因型。

结果

共纳入252例HIV感染者，其中75例合并感染TB且同时服用利福平。与HIV/TB组（1.52μg/mL，0.1557（μg/ml）/（mg/kg/d））相比，HIV组依非韦伦的C和C/D均更高（1.94μg/mL，0.2007（μg/ml）/（mg/kg/d））（P = 0.001）。516G>T和785A>G变异基因型患者的依非韦伦C/D显著更高（P<0.001），在516 GG、TT以及785 AA、AG基因型患者中，HIV/TB组的依非韦伦C/D显著低于HIV组（P<0.05）。