2022年我国部分省份抗病毒治疗前HIV-1整合酶抑制剂耐药流行情况

Prevalence of HIV-1 integrase inhibitor resistance before antiviral therapy in some provinces of China in 2022

目的了解大规模使用整合酶抑制剂前,我国HIV感染者抗病毒治疗前整合酶抑制剂耐药流行情况。方法参考WHO推荐使用的抗病毒治疗前耐药监测抽样方案,采用两阶段集群设计的横断面调查方法,通过系统抽样在我国9个省(市、自治区),收集部分2022年抗病毒治疗前HIV感染者血浆样本,提取病毒RNA,RT-PCR扩增整合酶区(IN)基因片段并测序,利用斯坦福大学耐药数据库对IN区进行耐药判定,分析HIV感染者抗病毒治疗前整合酶抑制剂的耐药流行情况。结果共获得来自9个省(市、自治区)的合格序列2851条,亚型分布以CRF07BC 1437人(50.4%)、CRF01AE 750人(26.3%)为主。整合酶抑制剂相关耐药突变的毒株有27株,耐药率约为0.95%,其中出现耐药较多的药物是RAL、EVG,分别为24例与26例,耐药株主要耐药突变位点为R263K(5例)、T66I/A(2例)、E138K(2例)、N155T/S(2例)、S147G(2例)、Q148K(2例)、Y143S(1例);次要位点包括G163K/N/R(4例)、S230R(3例)、V151A(2例)、S153F(2例)、H51Y(1例)。并且监测中还发现针对二代药物耐药的毒株,12例HIV感染者对DTG耐药,15例感染者对CAB耐药。结论我国2022年部分省份治疗前HIV感染者中整合酶抑制剂的耐药株流行水平较低。

ObjectiveTo investigate the prevalence of integrase inhibitor related resistance in HIV infected patients prior to initiating antiretroviral treatment(ART)in China before widespread use of integrase strand-transfer inhibitors(INSTIs).MethodsAccording to sampling guideline recommended by World Health Organization for the surveillance of drug resistance before ART,a cross-sectional study with two-stage clustering design was conducted.Through the systematic sampling in 9 provinces(cities,autonomous regions),some plasma samples from HIV infected patients before ART treatment were collected for extraction of viral RNA.The complete HIV integrase(IN)gene was amplified by RT-PCR and sequenced.The drug resistance was identified using Stanford HIV Drug Resistance Database.The prevalence of drug resistance to integrase inhibitor before ART among HIV infetected patients was analyzed.ResultsA total of 2851 qualified sequences were obtained from 9 provinces(cities,autonomous regions).In the term of subtype distribution,the dominant subtypes were CRF07_BC and CRF01_AE,accounting for 1437(50.4%)and 750(26.3%)cases,respectively.Twenty-seven strains were resistant to INSTIs and the rate of drug resistance was 0.95%.The strains were mainly resistant to RAL and EVG,accounting for 24 and 26 cases,respectively.The main drug resistance mutation sites were R263K(5 cases),T66I/A(2 cases),E138K(2 cases),N155T/S(2 cases),S147G(2 cases),Q148K(2 cases)and Y143S(1 case).The drug resistant strains of the second generation drugs were observed.Twelve patients were resistant DTG and 15 to CAB.ConclusionsThe overall prevalence of resistance strains of INSTIs among HIV infected patients before ART in some provinces of China in 2022 was low.