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中国北京初治患者中对HIV-1整合酶抑制剂的耐药性

Drug Resistance to HIV-1 Integrase Inhibitors Among Treatment-Naive Patients in Beijing, China.

作者信息

Yu Fengting, Li Qun, Wang Linghang, Zhao Hongxin, Wu Hao, Yang Siyuan, Tang Yunxia, Xiao Jiang, Zhang Fujie

机构信息

Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China.

Clinical Center for HIV/AIDS, Capital Medical University, Beijing, People's Republic of China.

出版信息

Pharmgenomics Pers Med. 2022 Mar 10;15:195-203. doi: 10.2147/PGPM.S345797. eCollection 2022.

Abstract

INTRODUCTION

Integrase strand transfer inhibitors (INSTIs) are important drugs that are currently used as the first line treatment for HIV-1 patients. The aim of this study was to characterize HIV-1 INSTI mutations among ART-naive patients in Beijing from 2019-2021.

METHODS

865 ART-naive patients were enrolled in this study between January 2019 and June 2021 in Beijing. The amplification of the entire pol gene containing the reverse transcriptase, protease and integrase regions was performed using a validated In-house SBS method. HIV-1 subtypes and circulating recombinant forms (CRFs) were determined using the COMET online tool (http://comet.retrovirology.lu). Stanford HIV-1 drug resistance database (HIVdb version 8.9) was used to analyze the mutations.

RESULTS

865 HIV-1 pol sequences were successfully amplified and sequenced. Among them, no major INSTI-related mutations were identified, but 12 polymorphic accessory mutations were found. Two patients have E138A and G163R mutations respectively and both could cause low-level resistance to RAL and EVG. Furthermore, one patient having S230R mutation resulted in low-level resistance to RAL, EVG, DTG and BIC.

CONCLUSION

The prevalence of INSTIs mutations remains low, which demonstrated that INSTIs have good applicability currently in our city. Nevertheless, it is very important to monitor the INSTI-related mutations in Beijing.

摘要

引言

整合酶链转移抑制剂(INSTIs)是目前用于治疗HIV-1患者的一线重要药物。本研究的目的是对2019年至2021年北京初治HIV-1患者中INSTI相关突变进行特征分析。

方法

2019年1月至2021年6月期间,在北京招募了865例初治患者。使用经过验证的内部SBS方法对包含逆转录酶、蛋白酶和整合酶区域的整个pol基因进行扩增。使用COMET在线工具(http://comet.retrovirology.lu)确定HIV-1亚型和循环重组形式(CRF)。利用斯坦福HIV-1耐药数据库(HIVdb版本8.9)分析突变情况。

结果

成功扩增并测序了865条HIV-1 pol序列。其中,未发现主要的INSTI相关突变,但发现了12个多态性辅助突变。两名患者分别有E138A和G163R突变,两者均可能导致对RAL和EVG的低水平耐药。此外,一名有S230R突变的患者对RAL、EVG、DTG和BIC产生低水平耐药。

结论

INSTIs突变的发生率仍然较低,这表明INSTIs目前在我市具有良好的适用性。然而,监测北京的INSTI相关突变非常重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9344/8922317/63d12802261a/PGPM-15-195-g0001.jpg

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