2017年贵州省中西部地区抗病毒治疗失败艾滋病患者HIV-1耐药水平研究
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摘要
目的分析贵州省中西部地区(贵阳、六盘水)一线抗病毒治疗失败艾滋病患者HIV-1耐药基因突变情况。方法采集贵州省一线抗病毒治疗时间>6个月,病毒载量≥1000 copies/ml的145例艾滋病患者血浆标本,提取血浆RNA,通过逆转录和巢式PCR扩增HIV-1 pol区基因,测序获得119例目的片段,提交美国斯坦福大学的网络HIV数据库进行耐药基因突变位点分析。结果在得到的119份pol区基因片段中,总耐药率为48.74%(58/119),包括NRTIs耐药突变30.25%(36/119),ABC、FTC、3TC耐药分别达28.57%(34/119);NNRTIs相关耐药突变46.22%(55/119),其中,EFV耐药占40.34%(48/119)、NVP耐药占42.86%(51/119);未检测到针对PIs发生耐药突变。发生NRTIs和NNRTIs交叉耐药占28.57%(34/119)。结论贵州省抗病毒治疗失败艾滋病患者HIV-1基因型耐药性比例高,类型复杂,因此应加强耐药监测,根据耐药突变情况及时调整抗病毒治疗方案,以减少耐药毒株的产生和传播。
Objective To analyze the mutations of HIV-1 drug resistant(HIVDR) genes in non-responders antiretroviral therapy(ART) in the middle and western regions in Guizhou Province which were in Guiyang and Liupanshui City in 2017. Methods Plasma specimens were collected from 145 people with AIDS/HIV who had been treated with ART for over 6 months and had a viral load over 1000 copies/ml. HIV-1 pol gene was amplified by RNA extraction, reverse transcription PCR(RT-PCR) and nested PCR. 119 cases of target fragments were sequenced successfully. It was analyzed the prevalence of mutations by Stanford University HIV drug resistance database. Results The total prevalence of HIV-1 drug resistance was 48.74%(58/119) in 119 gene fragments of pol region. The prevalence of NRTIs drug resistance was 30.25%(36/119), including 28.57%(34/119) respectively for ABC, FTC and 3 TC. The prevalence of NNRTIs related drug resistance was 46.22%(55/119), including EFV resistance 40.34%(48/119), NVP resistance 42.86%(51/119). No drug resistance was detected for PIs. The prevalence of NRTIs and NNRTIs cross-drug resistance accounted for 28.57%(34/119). Conclusion The HIV-1 drug resistance was highly prevalent among non-responders to ART in Guizhou with a complex pattern. So resistant monitoring should be strengthened and antiretroviral therapy regimens should be timely adjusted according to the drug-resistant mutations to reduce the generation of drug-resistant strains.
Objective To analyze the mutations of HIV-1 drug resistant(HIVDR) genes in non-responders antiretroviral therapy(ART) in the middle and western regions in Guizhou Province which were in Guiyang and Liupanshui City in 2017. Methods Plasma specimens were collected from 145 people with AIDS/HIV who had been treated with ART for over 6 months and had a viral load over 1000 copies/ml. HIV-1 pol gene was amplified by RNA extraction, reverse transcription PCR(RT-PCR) and nested PCR. 119 cases of target fragments were sequenced successfully. It was analyzed the prevalence of mutations by Stanford University HIV drug resistance database. Results The total prevalence of HIV-1 drug resistance was 48.74%(58/119) in 119 gene fragments of pol region. The prevalence of NRTIs drug resistance was 30.25%(36/119), including 28.57%(34/119) respectively for ABC, FTC and 3 TC. The prevalence of NNRTIs related drug resistance was 46.22%(55/119), including EFV resistance 40.34%(48/119), NVP resistance 42.86%(51/119). No drug resistance was detected for PIs. The prevalence of NRTIs and NNRTIs cross-drug resistance accounted for 28.57%(34/119). Conclusion The HIV-1 drug resistance was highly prevalent among non-responders to ART in Guizhou with a complex pattern. So resistant monitoring should be strengthened and antiretroviral therapy regimens should be timely adjusted according to the drug-resistant mutations to reduce the generation of drug-resistant strains.
引文
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[3] Coffin JM.HIV population dynamics in vivo:implications for genetic variation,pathogenesis,and therapy[J].Science,1995,267(5197):483-489.
[4] Phillips AN,Cambiano V,Miners A,et al.Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment:modelling study and economic analysis[J].Lancet HIV,2014,1(2):e85-93.
[5] Clutter DS,Jordan MR,Bertagnolio S,et al.HIV-1 drug resistance and resistance testing[J].Infect Genet Evol,2016,46:292-307.
[6] Kumarasamy N,Aga E,Ribaudo HJ,et al.Lopinavir/ritonavir monotherapy as second-lineantiretroviral treatment in resource-limited Settings:week 104 analysis of AIDS Clinical Trials Group(ACTG)A5230[J].Clin Infect Dis,2015,60(10):1552-1558.
[7] Prosperi MC,Mackie N,Di Giambenedetto S,et al.Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study[J].J AntimicrobChemother,2011,66(8):1886-1896.
[8] TenoRes Study G.Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection:a multicentre retrospectivecohort study[J].Lancet Infect Dis,2016,16(5):565-575.
[9] 中国疾病预防控制中心性病艾滋病预防控制中心.国家免费艾滋病抗病毒药物治疗手册[M].4版.北京:人民卫生出版社,2016.