广州市孕产妇人群HIV-1亚型分布和耐药特征分析
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摘要
目的了解广州市孕产妇人群艾滋病病毒1型(HIV-1)亚型和耐药情况。方法收集广州市2009—2014年孕产妇人群HIV-1抗体阳性样本,扩增蛋白酶(PR)和反转录酶(RT)基因序列,测序后构建系统进化树确定亚型,并与斯坦福大学HIV耐药数据库比对进行耐药分析。结果成功获得178份基因片段,其中10份为外籍病例;中国籍病例以CRF01_AE[42.86%(72/168)]和CRF07_BC[31.55%(53/168)]为主,外籍病例以C和CRF01_AE为主,各占30.00%(3/10)。中、外籍病例的亚型分布差异有统计学意义(P<0.001)。样本总体耐药突变率为12.36%(22/178),低度以上耐药率为5.62%(10/178),蛋白酶抑制剂(PIs)、核苷酸反转录酶抑制剂(NRTIs)和非核苷酸反转录酶抑制剂(NNRTIs)耐药率分别为2.81%(5/178)、1.12%(2/178)和2.25%(4/178)。耐药突变率最高的亚型为C亚型[50.00%(3/6)]。5例外籍病例携带耐药突变,其中3例为耐药病例。3.37%(6/178)样本被预测对单类药物呈高度耐药,未发现对多类药物呈高度耐药的样本。结论广州市HIV感染的孕产妇人群中有12种病毒亚型,以CRF01_AE和CRF07_BC为主,耐药突变率及耐药率低,但存在PIs或NRTIs或NNRTIs的高度耐药毒株且外籍病例具有较高耐药突变率和耐药率。
Objective To understand the subtype distribution and drug resistance of HIV-1 in HIV infected pregnant women in Guangzhou of Guangdong province.Methods Plasma samples from pregnant women who were positive for HIV-1 were collected during 2009–2014 for the amplification of protease(PR)and reverse transcriptase(RT)gene segments with nested reverse transcription polymerase chain reaction(nested-PCR).HIV subtypes were determined through phylogenetic analysis and the drug resistance mutation(DRM)was analyzed with HIV Drug Resistance Database of Stanford University.Results A total of 178 gene segments,including 10 from foreign cases,were successfully amplified.Significant difference in subtype distribution was observed between domestic cases and foreign cases(P<0.001),the predominant subtypes were CRF01_AE(42.86%,72/168)and CRF07_BC(31.55%,53/168)in domestic cases and the predominant subtypes were C(30.00%,3/10)and CRF01_AE(30.00%,3/10)in foreign cases.The incidence rate of DRM was 12.36%.The upper low level resistant rates to any drug was 5.62%(10/178),and the resistant rates to protease inhibitors(PIs),nucleoside reverse transcriptase inhibitors(NRTIs),non-nucleoside reverse transcriptase inhibitors(NNRTIs)were 2.81%(5/178),1.12%(2/178)and 2.25%(4/178),respectively.Subtype C showed the highest DRM rate(50.00%,3/6).DRMs were observed in 5 foreign cases and 3 cases were drug resistant.Six samples(3.37%)were predicted to be highly resistant to single class drug.No samples which were highly resistant to multi-class drugs were detected.Conclusion Twelve HIV-1 subtypes were detected in HIV infected pregnant women in Guangzhou,the predominant subtypes were CRF01_AE and CRF07_BC.The DRM rate and drug resistant rate were low,but the strains with high resistance to PIs or NRTIs or NNRTIs were observed and the foreign cases had higher DRM rate and drug resistant rate.
Objective To understand the subtype distribution and drug resistance of HIV-1 in HIV infected pregnant women in Guangzhou of Guangdong province.Methods Plasma samples from pregnant women who were positive for HIV-1 were collected during 2009–2014 for the amplification of protease(PR)and reverse transcriptase(RT)gene segments with nested reverse transcription polymerase chain reaction(nested-PCR).HIV subtypes were determined through phylogenetic analysis and the drug resistance mutation(DRM)was analyzed with HIV Drug Resistance Database of Stanford University.Results A total of 178 gene segments,including 10 from foreign cases,were successfully amplified.Significant difference in subtype distribution was observed between domestic cases and foreign cases(P<0.001),the predominant subtypes were CRF01_AE(42.86%,72/168)and CRF07_BC(31.55%,53/168)in domestic cases and the predominant subtypes were C(30.00%,3/10)and CRF01_AE(30.00%,3/10)in foreign cases.The incidence rate of DRM was 12.36%.The upper low level resistant rates to any drug was 5.62%(10/178),and the resistant rates to protease inhibitors(PIs),nucleoside reverse transcriptase inhibitors(NRTIs),non-nucleoside reverse transcriptase inhibitors(NNRTIs)were 2.81%(5/178),1.12%(2/178)and 2.25%(4/178),respectively.Subtype C showed the highest DRM rate(50.00%,3/6).DRMs were observed in 5 foreign cases and 3 cases were drug resistant.Six samples(3.37%)were predicted to be highly resistant to single class drug.No samples which were highly resistant to multi-class drugs were detected.Conclusion Twelve HIV-1 subtypes were detected in HIV infected pregnant women in Guangzhou,the predominant subtypes were CRF01_AE and CRF07_BC.The DRM rate and drug resistant rate were low,but the strains with high resistance to PIs or NRTIs or NNRTIs were observed and the foreign cases had higher DRM rate and drug resistant rate.
引文
[1]李燕,徐慧芳,赵宇腾,等.1998-2006年广州市HIV感染孕产妇母婴传播干预情况分析[J].中国艾滋病性病,2008,14(1):62-63.DOI:10.3969/j.issn.1672-5662.2008.01.022.Li Y,Xu HF,Zhao YT,et al.Analysis of intervention services for HIV-infected pregnant women in Guangzhou from 1998 to2006[J].Chin J AIDS STD,2008,14(1):62-63.DOI:10.3969/j.issn.1672-5662.2008.01.022.
[2]杨丽,于佳,邹兴文.广州市41例HIV感染孕产妇干预情况分析[J].中国艾滋病性病,2014,20(5):340-342.DOI:10.13419/j.cnki.aids.2014.05.015.Yang L,Yu J,Zou XW.Analysis of intervention service for 41HIV-infected pregnant women in Guangzhou[J].Chin J AIDSSTD,2014,20(5):340-342.DOI:10.13419/j.cnki.aids.2014.05.015.
[3]中国疾病预防控制中心性病艾滋病预防控制中心.2017年12月全国艾滋病性病疫情[J].中国艾滋病性病,2018,24(2):111.DOI:10.13419/j.cnki.aids.2018.02.01.National Center for AIDS/STD Control and Prevention,Chinese Center for Disease Control and Prevention.Update on the AIDS/STD epidemic in China in December 2017[J].Chin J AIDSSTD,2018,24(2):111.DOI:10.13419/j.cnki.aids.2018.02.01.
[4]Siegfried N,van der Merwe L,Brocklehurst P,et al.Antiretrovirals for reducing the risk of mother-to-child transmission of HIVinfection[J].Cochrane Database Syst Rev,2011(7):CD003510.DOI:10.1002/14651858.CD003510.pub3.
[5]韩志刚,吴昊,梁彩云,等.广州市2008-2010年和2015年外籍HIV-1感染者病毒亚型分析[J].中华流行病学杂志,2017,38(6):805-809.DOI:10.3760/cma.j.issn.0254-6450.2017.06.023.Han ZG,Wu H,Liang CY,et al.Distribution of HIV-1 subtypes among foreign patients,in Guangzhou,between 2008 and 2010,and in 2015[J].Chin J Epidemiol,2017,38(6):805-809.DOI:10.3760/cma.j.issn.0254-6450.2017.06.023.
[6]石向东,张强,王晓辉,等.深圳市HIV-1感染孕产妇淋巴细胞亚群变化和毒株亚型分布特征[J].现代预防医学,2010,37(13):2419-2421.Shi XD,Zhang Q,Wang XH,et al.The changes of lymphocyte subsets and the distribution of hiv-1 subtypes in HIV-1 infected pregnant women in Shenzhen[J].Mod Prev Med,2010,37(13):2419-2421.
[7]何浩岚,许飞龙,蔡卫平,等.广东省HIV-1分子流行病学分析[J].广东医学,2012,33(22):3471-3474.DOI:10.3969/j.issn.1001-9448.2012.22.047.He HL,Xu FL,Cai WP,et al.Molecular epidemiology analysis of HIV-1 in Guangdong province[J].Guangdong Med J,2012,33(22):3471-3474.DOI:10.3969/j.issn.1001-9448.2012.22.047.
[8]Han J,Wang L,Jiang Y,et al.Resistance mutations in HIV-1infected pregnant women and their infants receiving antiretrovirals to prevent HIV-1 vertical transmission in China[J].Int J STDAIDS,2009,20(4):249-254.DOI:10.1258/ijsa.2008.008480.
[9]钟活麟,梁志伟,蔡卫平,等.2011-2012年广东省人类免疫缺陷病毒/获得性免疫缺陷综合征患者的耐药情况分析[J].中国药物经济学,2015,10(7):72-74.Zhong HL,Liang ZW,Cai WP,et al.In Guangdong drug resistance of patients with human immunodeficiency virus/acquired immunodeficiency syndrome in 2011 and 2012[J].China JPharm Econ,2015,10(7):72-74.
[10]陈敏,贾曼红,王继宝,等.云南省66例孕产妇的HIV-1基因型和耐药传播水平[J].中华疾病控制杂志,2014,18(12):1199-1202.Chen M,Jia MH,Wang JB,et al.HIV-1 genotype and its transmitted drug resistance among pregnant women in Yunnan Province[J].Chin J Dis Control Prev,2014,18(12):1199-1202.
[11]Guo JL,Yan Y,Zhang JF,et al.Genetic characterization and antiretroviral resistance mutations among treatment-naive HIV-infected individuals in Jiaxing,China[J].Oncotarget,2017,8(11):18271-18279.DOI:10.18632/oncotarget.15382.
[12]Li HP,Chang S,Han Y,et al.The prevalence of drug resistance among treatment-naive HIV-1-infected individuals in China during pre-and post-2004[J].BMC Infect Dis,2016,16(1):605.DOI:10.1186/s12879-016-1928-x.
[2]杨丽,于佳,邹兴文.广州市41例HIV感染孕产妇干预情况分析[J].中国艾滋病性病,2014,20(5):340-342.DOI:10.13419/j.cnki.aids.2014.05.015.Yang L,Yu J,Zou XW.Analysis of intervention service for 41HIV-infected pregnant women in Guangzhou[J].Chin J AIDSSTD,2014,20(5):340-342.DOI:10.13419/j.cnki.aids.2014.05.015.
[3]中国疾病预防控制中心性病艾滋病预防控制中心.2017年12月全国艾滋病性病疫情[J].中国艾滋病性病,2018,24(2):111.DOI:10.13419/j.cnki.aids.2018.02.01.National Center for AIDS/STD Control and Prevention,Chinese Center for Disease Control and Prevention.Update on the AIDS/STD epidemic in China in December 2017[J].Chin J AIDSSTD,2018,24(2):111.DOI:10.13419/j.cnki.aids.2018.02.01.
[4]Siegfried N,van der Merwe L,Brocklehurst P,et al.Antiretrovirals for reducing the risk of mother-to-child transmission of HIVinfection[J].Cochrane Database Syst Rev,2011(7):CD003510.DOI:10.1002/14651858.CD003510.pub3.
[5]韩志刚,吴昊,梁彩云,等.广州市2008-2010年和2015年外籍HIV-1感染者病毒亚型分析[J].中华流行病学杂志,2017,38(6):805-809.DOI:10.3760/cma.j.issn.0254-6450.2017.06.023.Han ZG,Wu H,Liang CY,et al.Distribution of HIV-1 subtypes among foreign patients,in Guangzhou,between 2008 and 2010,and in 2015[J].Chin J Epidemiol,2017,38(6):805-809.DOI:10.3760/cma.j.issn.0254-6450.2017.06.023.
[6]石向东,张强,王晓辉,等.深圳市HIV-1感染孕产妇淋巴细胞亚群变化和毒株亚型分布特征[J].现代预防医学,2010,37(13):2419-2421.Shi XD,Zhang Q,Wang XH,et al.The changes of lymphocyte subsets and the distribution of hiv-1 subtypes in HIV-1 infected pregnant women in Shenzhen[J].Mod Prev Med,2010,37(13):2419-2421.
[7]何浩岚,许飞龙,蔡卫平,等.广东省HIV-1分子流行病学分析[J].广东医学,2012,33(22):3471-3474.DOI:10.3969/j.issn.1001-9448.2012.22.047.He HL,Xu FL,Cai WP,et al.Molecular epidemiology analysis of HIV-1 in Guangdong province[J].Guangdong Med J,2012,33(22):3471-3474.DOI:10.3969/j.issn.1001-9448.2012.22.047.
[8]Han J,Wang L,Jiang Y,et al.Resistance mutations in HIV-1infected pregnant women and their infants receiving antiretrovirals to prevent HIV-1 vertical transmission in China[J].Int J STDAIDS,2009,20(4):249-254.DOI:10.1258/ijsa.2008.008480.
[9]钟活麟,梁志伟,蔡卫平,等.2011-2012年广东省人类免疫缺陷病毒/获得性免疫缺陷综合征患者的耐药情况分析[J].中国药物经济学,2015,10(7):72-74.Zhong HL,Liang ZW,Cai WP,et al.In Guangdong drug resistance of patients with human immunodeficiency virus/acquired immunodeficiency syndrome in 2011 and 2012[J].China JPharm Econ,2015,10(7):72-74.
[10]陈敏,贾曼红,王继宝,等.云南省66例孕产妇的HIV-1基因型和耐药传播水平[J].中华疾病控制杂志,2014,18(12):1199-1202.Chen M,Jia MH,Wang JB,et al.HIV-1 genotype and its transmitted drug resistance among pregnant women in Yunnan Province[J].Chin J Dis Control Prev,2014,18(12):1199-1202.
[11]Guo JL,Yan Y,Zhang JF,et al.Genetic characterization and antiretroviral resistance mutations among treatment-naive HIV-infected individuals in Jiaxing,China[J].Oncotarget,2017,8(11):18271-18279.DOI:10.18632/oncotarget.15382.
[12]Li HP,Chang S,Han Y,et al.The prevalence of drug resistance among treatment-naive HIV-1-infected individuals in China during pre-and post-2004[J].BMC Infect Dis,2016,16(1):605.DOI:10.1186/s12879-016-1928-x.