保定市新诊断HIV感染者整合酶抑制剂原发耐药分析

Primary Drug Resistance to Integrase Inhibitors Among Newly Diagnosed HIV Infected Patients in Baoding City

目的了解保定地区2020年新报告人类免疫缺陷病毒1型(HIV-1)感染者整合酶抑制剂(integrase inhibitors,INIs)原发耐药情况,为治疗提供参考依据。方法收集保定市人民医院2020年1月至2020年12月经本市疾控新确证的未接受过含整合酶抑制剂(INIs)抗病毒治疗的96例HIV-1感染者的外周血样本,采用In-House方法,对血浆样本进行pol基因区扩增并测序,将拼接好的序列提交至美国斯坦福大学的HIV耐药数据库,分析整合酶(IN)区耐药突变位点及耐药程度。结果由于样本质量问题,扩增失败13例,共获得83份样本的HIV-1 pol区基因片段,基因亚型包括CRF01_AE 45例(54.2%),B亚型13例(15.7%),B+C亚型10例(12.0%),CRF07_BC 11例(13.3%),C亚型2例(2.4%),CRF55_01B 1例(1.2%),A亚型1例(1.2%)。8例存在IN区耐药突变位点,其中6例表现出对INIs耐药,INIs原发耐药率为7.2%,全部INIs耐药毒株均属于交叉耐药。其中IN区主要突变位点R263K、G140S、S147SG、E138A;IN区次要突变位点H51Y、A128AT、S153SF、A49AG、P145P、Q146QL,引起了拉替拉韦(Raltegravir,RAL)、埃替格韦(Elvitegravir,EVG)、多替拉韦(Dolutegravir,DTG)、贝克他韦(Bictegravir,BIC)四种INIs不同程度的耐药。结论保定地区新诊断HIV-1感染者中,存在原发性INIs基因突变,INIs原发耐药率为7.2%,应加强IN区耐药监测,合理调整INIs的用药方案。

Objective To understand the primary drug resistance of integrase inhibitors in the newly reported human immunodeficiency virus type 1(HIV-1)infection in Baoding area in 2020,and to provide a reference for treatment.Methods We collected peripheral blood samples of 96 HIV-1 infected patients who had not received antiviral treatment containing integrase inhibitors(INIs)and had been newly confirmed by the city’s disease control from January,2020 to December,2020 in Baoding People’s Hospital.In-House method was applied to amplify and sequence the pol gene region of plasma samples,and we submitted the spliced sequence to the HIV drug resistance database of Stanford University in the United States,and then analyzed the integrase(IN)region drug resistance mutation site and the degree of drug resistance.Results Due to sample quality problems,13 cases of amplification failed,and a total of 83 samples of HIV-1 pol region gene fragments were obtained.The genotypes included 45 cases of CRF01_AE(54.2%),13 cases of B subtype(15.7%),10 cases of B+C subtype(12.0%),11 cases of CRF07_BC(13.3%),2 cases of C subtype(2.4%),1 case of CRF55_01B(1.2%),and 1 case of A subtype(1.2%).8 cases had primary integrase region resistant mutation sites,of which 6 cases showed primary resistances to integrase inhibitors,and all INIs resistant strains belonged to cross-resistance.Among them,the main mutation sites in the IN region were R263K,G140S,S147SG,and E138A,and the secondary mutation sites in the IN region were H51Y,A128AT,S153SF,A49AG,P145P,and Q146QL,which caused resistant to lategravir(RAL),Elvitegravir(EVG),Dolutegravir(DTG)and Bictegravir(BIC)at varying degrees.The primary resistance rate of integrase inhibitors was 7.2%.Conclusion Among the HIV-1 infected persons who have not been treated with integrase inhibitors in Baoding area,there are primary INIs gene mutations,and the primary drug resistance rate of HIV-1 infected persons is 7.2%.The monitoring of drug resistance in the IN area should be strengthened and adjusted rationally,as well as the medication regimen of INIs.