阜新市HIV-1感染者和AIDS患者原发性整合酶基因耐药突变分析

Analysis of resistance mutations of primary integrase gene in HIV-1 infected cases and AIDS patients in Fuxin City

目的了解阜新市HIV感染者和AIDS患者整合酶基因的变异情况,分析阜新市原发性整合酶基因突变及相关耐药情况,为治疗提供参考依据。方法收集2018年-2019年阜新市102例HIV-1感染者和AIDS患者外周静脉血,分离血浆,-80℃冻存备用。采用反转录巢式聚合酶链式反应扩增病毒pol基因区并进行序列测定,分析IN区耐药突变位点及其耐药程度。结果在102例样本中,扩增并得到有效整合酶基因序列的共有72例。共发现4种基因亚型,其中CRF01_AE为主要亚型,占79.2%(57/72),其次是07BC亚型,占12.5%(9/72),其余3种亚型:B亚型3例、G亚型1例、65_CPX亚型2例。检出1例对整合酶抑制剂雷特格韦(raltegravir,RAL)和埃替格韦(elvitegravir,EVG)具有较低耐药能力,占1.39%(1/72),其耐药相关突变位点是E138A。不同CD4水平,不同治疗时间患者的整合酶基因变异率差异有统计学意义(P <0.01)。结论阜新市不同HIV-1基因亚型中,整合酶耐药突变现象和基因多态性具有相应的区别,需要对整合酶基因序列特征进行研究,掌握基线数据,从而为更好地开展抗病毒治疗提供科学依据。

Objective To investigate the variation of integrase gene in HIV infected cases and AIDS patients in Fuxin City,and analyze the mutation of primary integrase gene and related drug resistance,so as to provide basis for treatment. Methods A total of 102 HIV-1 infected cases and AIDS patients in Fuxin from 2018 to 2019 were collected and the plasma was separated and frozen at-80 ℃.The pol gene region of the virus was amplified by reverse transcription nested polymerase chain reaction(RT-PCR) for gene sequence. Results Seventy-two of one hundred samples were amplified and integrase gene sequences were obtained. Four genotypes were found,of which CRF01_AE subtype was the main subtype,accounting for 79. 2%(57/72),followed by 07BC subtype,accounting for 12. 5%(9/72). The other subtypes were B subtype,G subtype and 65_CPX subtype. One case was found to have low resistance to raltegravir and elvitegravir,accounting for 1. 39%(1/72),and its resistance related mutation site was E138 A. There was statistical significance on the difference in the variation rate of integrase gene among the patients with different CD4 levels and different treatment time(P < 0. 01). Conclusion In different HIV-1 genotypes of Fuxin City,there are differences between integrase resistance mutation and gene polymorphism. It is necessary to investigate the characteristics of integrase gene and the baseline data to provide scientific basis for better antiviral treatment.