广西胸科医院2019年抗逆转录病毒治疗失败患者HIV-1基因型耐药分析

Analysis of genotypic drug resistance among HIV-1 patients with virological failure after antiretroviral therapy in Guangxi Chest Hospital in 2019

目的分析2019年广西胸科医院抗逆转录病毒治疗(antiretroviral therapy,ART)病毒抑制失败患者HIV-1基因型耐药发生水平及特征。方法收集2019年1月1日—12月31日接受ART≥6个月且病毒载量≥1000 copies/mL的成人病毒抑制失败患者血浆提取核酸,采用美国雅培ViroSeq方法进行基因型耐药检测。结果共有131例病毒抑制失败患者获得pol基因片段序列。74例(56.5%)对至少一类病毒抑制剂耐药。核苷类逆转录酶抑制剂(nucleoside reverse transcriptase inhibitors,NRTIs)和非核苷类逆转录酶抑制剂(non-NRTIs,NNRTIs)最常见的突变位点分别为M184(42.0%)和K103(37.4%)。8例(6.1%)和15例(11.5%)分别对NRTIs和NNRTIs产生单类药物耐药,49例(37.4%)对NRTIs和NNRTIs产生双重耐药,1例(0.8%)对NRTIs、NNRTIs和蛋白酶抑制剂PIs产生三重耐药。多因素logistic回归分析显示,与耐药发生存在显著性关联的因素有治疗前CD4+T淋巴细胞计数<200个/μl(AOR=4.57,95%CI:1.28~16.30)、抗病毒治疗时间6~35个月(AOR=12.87,95%CI:3.36~49.33)及≥60个月(AOR=5.95,95%CI:1.75~20.22)。对常用药物拉米夫定(3TC)、齐多夫定(AZT)、替诺福韦(TDF)、阿巴卡韦(ABC)、利匹韦林(RPV)、依非韦伦(EFV)、奈韦拉平(NVP)和洛匹那韦/利托那韦(LPV/r)的获得性耐药所占比例分别为39.7%、6.9%、10.7%、19.1%、6.9%、45.0%、49.6%和1.5%。结论广西胸科医院56.5%的ART病毒抑制失败患者出现获得性耐药,超过1/3病例同时对NRTIs和NNRTIs双重耐药。定期随访评价治疗效果,加强依从性教育,对耐药发生病例及时更换治疗药物方案,提高ART效果。

Objective To analyze the prevalence and characteristics of genotypic drug resistance among HIV-1 infected patients experiencing viral suppression failure after antiretroviral therapy(ART)in Guangxi Chest Hospital in 2019.Methods Nucleic acids were purified from plasma samples collected from adult patients who had received ART for 6 months or more in 2019 with viral load≥1000 copies/mL.The ViroSeq method was used to detect genotypic drug resistance.Results The HIV-1 pol gene sequences were obtained from 131 patients who failed in viral suppression.Seventy-four patients(56.5%)were resistant to at least one antiviral drug.The most common mutations resulting in drug resistance to nucleoside reverse transcriptase inhibitors(NRTIs)and non-nucleoside reverse transcriptase inhibitors(NNRTIs)were M184(42.0%)and K103(37.4%),respectively.There were 8 cases(6.1%)and 15 cases(11.5%)with single drug resistance to NRTIs and NNRTIs,respectively.Forty-nine cases(37.4%)showed drug resistance to both NRTIs and NNRTIs,and 1 case(0.8%)had triple drug resistance to NTRIs,NNTRIs and protein inhabitators.Multivariate logistic regression model showed that the factors significantly correlated with drug resistance were CD4<200/μl before treatment(AOR=4.57,95%CI:1.28-16.30),ART treatment from 6 months to 35 months(AOR=12.87,95%CI:3.36-49.33)and over 60 months(AOR=5.95,95%CI:1.75-20.22).The proportions of acquired resistance to common drugs,including lamivudine(3TC),zidovudine(AZT),tenofovir(TDF),abacavir(ABC),rilpivirine(RPV),efavirenz(EFV),nevirapine(NVP)and lopinavir/ritonavir(LPV/r)in the patients with viral suppression failure were 39.7%,6.9%,10.7%,19.1%,6.9%,45.0%,49.6%,and 1.5%,respectively.Conclusions Acquired drug resistance occurred in 56.5%of the patients with virological failure in Guangxi Chest Hospital,and more than one third of the patients showed dual resistant to NRTIs and NNRTIs.Regular follow-up should be carried out for therapeutic efficacy evaluation and compliance education should be enhanced.The theraprtic program should be modified in time in case of drug resistance to improve the ART efficiency.