广州抗逆转录病毒治疗后低水平HIV-1病毒载量感染者基因型耐药特征分析

Characteristics of genotypic drug resistance for HIV-1 infected patient with low viral load after antiretroviral therapy in Guangzhou

目的分析广州市抗逆转录病毒治疗(antiretroviral therapy,ART)后HIV-1病毒载量介于50~200 copies/mL的感染者基因型耐药发生特征。方法募集2023年1月至7月广州医科大学附属市八医院感染门诊接受ART满6个月,且HIV-1病毒载量介于50~200 copies/mL的感染者。用0.5 mL血浆于4℃超速离心浓缩病毒后提取RNA,经逆转录和巢式PCR扩增HIV-1 pol基因片段。获得基因序列经COMET HIV-1进行分型,并用Mega 11构建系统邻接法进化树验证亚型。经斯坦福HIV耐药数据库解析耐药发生情况。结果共随访11799例感染者,发现415例(3.5%)低水平病毒载量感染者。从完成检测的297例感染者中扩增获得154条pol基因片段序列(52.0%)。主要基因亚型为CRF01-AE(34.4%,53/154)和CRF07-BC(31.2%,48/154)。耐药相关突变(drug resistance mutations,DRMs)发生率为37.0%(57/154),最常见的DRMs为非核苷类逆转录酶抑制剂(NNRTIs)突变V179E(11.7%,18/154)和核苷类逆转录酶抑制剂(NRTIs)突变S68G(6.5%,10/154)和M184V(5.2%,8/154)。对任一药物耐药发生率为17.5%(27/154),其中NVP耐药率为11.7%(18/154),EFV耐药率为11.0%(17/154),RPV耐药率为10.4%(16/154)。结论广州ART后低水平病毒载量感染者耐药相关突变发生率较高(18.2%~37.0%),对我国常用的一线抗病毒药物存在不同程度耐药。应加强治疗后低病毒载量感染者的耐药监测,以优化治疗方案、改善临床结果。

Objective To analyze the characteristics of developing genotypic drug resistance(DR)among HIV-1 infected patients with viral load(VL)ranging from 50 to 200 copies/mL after antiretroviral therapy(ART)in Guangzhou.Methods HIV-1 infected patients were recruited who received ART for 6 months at the Guangzhou Eighth People's Hospital from January to July 2023,with VL of 50-200 copies/mL.Plasma sample of 0.5 mL was ultracentrifuged at 4℃for concentration of virus.The RNA was extracted and HIV-1 pol gene fragment was amplified by reverse transcriptase PCR(RT-PCR)and nested PCR.The obtained sequences were used for genotyping using COMET HIV-1 subtyping tool.The neighbor-joining tree was constructed using MEGA 11 software to validate the subtypes.The Stanford HIVdb Program was used to interpret the drug resistance.Results A total of 11799 infected patients were followed up,and 415(3.5%)cases had VL ranging from 50 to 200 copies/mL.Among the 297 patients who completed RT-PCR testing,154 partial pol gene sequences were obtained(52.0%).The main subgenotypes were CRF01-AE(34.4%,53/154)and CRF07-BC(31.2%,48/154).Fifty-seven cases(37.0%,57/154)carried drug resistant mutations(DRMs).The most common DRMs were non-nucleoside reverse transcriptase inhibitors(NNRTIs)related mutation V179E(11.7%,18/154),NRTIs related mutations S68G(6.5%,10/154)and\M184V(5.2%,8/154).The DM rate to any drug was 17.5%(27/154),and the DM rates were 11.7%(18/154)to NVP,11.0%(17/154)to EFV,and 10.4%(16/154)to RPV.Conclusions The infected patient with low VL after ART had hgh prevalence(18.2%-37.0%)of DRMs and developed resistance to many current first-line ART drugs in China to a different degree.The profile of DR among patients with low VL after treatment should be well monitored,to assist optimization of treatment regimens and improvement of clinical outcomes.