吉林省抗病毒治疗失败HIV/AIDS患者HIV-1毒株基因型耐药特征

Genotype resistance characteristics of HIV-1 strains in HIV/AIDS patients who failed in antiviral therapy in Jilin Province

目的了解吉林省重点地区抗病毒治疗失败的HIV/AIDS患者HIV-1基因型及耐药性特征,分析HIV-1感染者治疗失败的原因。方法2019—2021年,采集吉林省抗病毒治疗时间超过12个月,血浆中HIV-1病毒载量≥1000拷贝/ml的HIV/AIDS患者血液样本,用PCR法扩增HIV-1 pol基因,构建最大似然系统进化树以确认基因亚型。使用斯坦福大学HIV耐药性数据库分析耐药突变位点和特征。结果从330例患者样本中成功扩增pol基因,其中男性290例(87.9%),平均年龄(33.6±11.4)岁,多以同性性传播感染为主,占64.8%。总耐药率达到58.8%。基因型主要为CRF01_AE亚型,占58.2%;B亚型占15.2%,CRF07_BC亚型占10.0%。蛋白酶抑制剂(PI)、核苷类逆转录酶抑制剂(NRTI)和非核苷类逆转录酶抑制剂(NNRTI)的耐药比例分别为3.0%、42.1%和67.0%。多因素回归分析显示,相对于首次CD4+T细胞计数低于200个/μl的患者,200个/μl以上患者耐药发生风险降低。相对于感染CRF01_AE亚型,B亚型感染人群的耐药发生风险较高;相对于≤20岁感染者,20岁以上感染者的耐药发生风险较高。结论吉林省重点地区抗病毒治疗失败的患者中,耐药性突变更频繁地出现在NNRTI中。要加强对首次CD4+T细胞计数低于200个/μl、病毒为B亚型患者以及20岁以上感染人群的耐药监测,确保治疗过程的持续性和高效性。

Objective To analyze the genotype and drug resistance characteristics of HIV-1 strains among infected patients who failed in antiretroviral therapy in key regions of Jilin.Methods The blood samples of HIV/AIDS patients with plasma viral load≥1000 copies/ml who had been on antiviral treatment for more than 12 months in Jilin Province were collected to amplify HIV-1 pol gene.A maximum likelihood phylogenetic tree was constructed to confirm the genotype.Resistance mutation loci and resistance profiles were analyzed using the Stanford University HIV Drug Resistance Database.Results Pol gene was successfully amplified from 330 cases samples.Among them,290 cases(87.9%)were male,with an average age of(33.6±11.4)years old,most of them were sexually transmitted infections,accounted for 64.8%.The total drug resistance rate was 58.8%.The main genotypes were CRF01_AE subtype(58.2%),B subtype(15.2%)and CRF07_BC subtype(10.0%).The resistance rates of protease inhibitors(PI),nucleoside reverse transcriptase inhibitors(NRTI)and non-nucleoside reverse transcriptase inhibitors(NNRTI)were 3.0%,42.1%and 67.0%,respectively.Multivariate regression analysis showed that patients with initial CD4+T cells count less than 200 cells/μl had a higher risk of resistance than those of more than 200 cells/μl.In addition,compared with CRF01_AE subtype,the cases infected with subtype B had a higher risk of drug resistance,the risk factors of drug resistance were higher in people over 20 years old compared with those≤20 years old.Conclusion In the cases who failed in antiviral therapy in key areas of Jilin Province,resistance mutations appeared more frequently in NNRTI.The monitoring of resistance should be strengthened in the patients with initial CD4+T cells count less than 200 cells/μl or subtype B virus infections,and infected people over the age of 20,to ensure the continuity and efficiency of treatment.