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
凌雪梅 1林雅晴 2李凌华 1李俊彬 1李全敏 1曾琨 2张楚瑜 2兰芸2
作者信息
- 1. 广州医科大学附属市八医院感染病中心 510440
- 2. 广州医科大学附属市八医院传染病研究所 510440
- 折叠
摘要
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11 799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.
Abstract
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 11 799 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.
关键词
人免疫缺陷病毒/抗逆转录病毒治疗/低病毒载量/基因型耐药Key words
Human immunodeficiency virus/Antiretroviral therapy/Low viral load/Genotypic drug resistance引用本文复制引用
出版年
2024