中国艾滋病病毒耐药现状
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摘要
艾滋病病毒(HIV)耐药产生和传播将妨碍抗逆转录病毒治疗(ART)防控艾滋病的策略的实施。我国从开展免费抗病毒治疗以来,逐步推进HIV耐药监测和检测活动,形成HIV检测监测相结合耐药防控方案。中国目前主要开展传播性耐药监测、治疗前耐药和治疗后耐药评估等。全国多数地区传播性耐药处于低水平,治疗前非核苷类反转录酶抑制剂(NNRTI)的耐药流行率低于10%。病毒学失败患者约半数以上存在耐药突变。目前我国HIV耐药相对较低,部分地区耐药增加趋势,需进一步规范实施耐药监测评估。
The emergence and spread of drug resistant HIV strains can compromise the strategy of using antiretroviral drugs for treating and preventing HIV infection. HIV drug resistance surveillance and monitoring program have been gradually conducted since 2003. The HIV drug resitance operational framework was developed which including HIV drug resistance. Currently, China is mainly engaged in the surveilance of transmitted HIV drug resistance(TDR), pretreatment drug resistance(PDR) in na?ve patients and acquired drug resistance(ADR) in individuals on ART. In most areas of China, the prevalence of TDR is relatively low, and the prevalence of non-nucleoside reverse transcriptase inhibitors(NNRTI) PDR is lower than 10%. The prevalence of HIV-1 DR in participants experiencing treatment failure is about 50%.The prevalence of HIV drug resistance is relatively low in China. However, with the increasing number of people receiving antiviral treatment, drug resistance rate increased in some regions. It is important to standardize surveillance and monitoring HIV drug resistance.
The emergence and spread of drug resistant HIV strains can compromise the strategy of using antiretroviral drugs for treating and preventing HIV infection. HIV drug resistance surveillance and monitoring program have been gradually conducted since 2003. The HIV drug resitance operational framework was developed which including HIV drug resistance. Currently, China is mainly engaged in the surveilance of transmitted HIV drug resistance(TDR), pretreatment drug resistance(PDR) in na?ve patients and acquired drug resistance(ADR) in individuals on ART. In most areas of China, the prevalence of TDR is relatively low, and the prevalence of non-nucleoside reverse transcriptase inhibitors(NNRTI) PDR is lower than 10%. The prevalence of HIV-1 DR in participants experiencing treatment failure is about 50%.The prevalence of HIV drug resistance is relatively low in China. However, with the increasing number of people receiving antiviral treatment, drug resistance rate increased in some regions. It is important to standardize surveillance and monitoring HIV drug resistance.
引文
[1]国家卫健委.艾滋病感染者125万属低流行水平[EB/OL].[2018-11-2319:23:00].http://news.cctv.com/2018/11/23/ARTIQCG9T14qj5yy8jI689BL181123.shthl,2018.
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[3]Zhang F,Dou Z,Ma Y,et al.Five-year outcomes of the China National Free Antiretroviral Treatment Program[J].Ann Intern Med,2009,151(4):241-251.
[4]Jia Z,Mao Y,Zhang F,et al.Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China(2003-11):a national observational cohort study[J].Lancet,2013,382(9899):1195-1203.
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[12]Li JY,Li HP,Li L,et al.Prevalence and evolution of drug resistance HIV-1 variants in Henan,China[J].Cell Res,2005,15(1):843-849.
[13]Ma Y,Zhang F,Li H,et al.Monitoring HIV drug resistance using early warning indicators in China:results from a pilot survey conducted in 2008[J].Clin Infect Dis,2012,54(Suppl 4):S300-S302.
[14]Shafer RW,Rhee SY,Pillay D,et al.HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance[J].AIDS,2007,21(2):215-223.
[15]Jordan MR,Bennett DE,Bertagnolio S,et al.World Health Organization surveys to monitor HIV drug resistance prevention and associated factors in sentinel antiretroviral treatment sites[J].Antivir Ther,2008,13(Suppl 2):15-23.
[16]WHO.HIV Fact sheet.Updated July 2017[EB/OL].Avaliable at:http://www.who.int/mediacentre/factsheets/fs360/en/.
[17]吴亚松,马烨.HIV耐药评估和预防策略[J].传染病信息,2017,30(6):351-4.
[18]Liao L,Xing H,Dong Y,et al.Surveys of transmitted HIV drug resistance in 7 geographic Regions in China,2008-2009[J].Clin Infect Dis,2012,54(Suppl 4):S320-323..
[19]陈敏,王继宝,邢辉,等.云南省德宏傣族景颇族自治州2015年HIV-1耐药传播警戒线调查[J].中华流行病学杂志,2017,38(7):959-962.
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[22]孙晓光,于海英,苏生利,等.山东省2013-2015年新发现未治疗HIV-1感染者耐药毒株传播警戒线调查[J].中华预防医学杂志,2017,51(7):604-609.
[23]吴可可,苏德华,吴矛矛.温州地区未治疗AIDS病人的HIV毒株耐药基因变异研究[J].中国艾滋病性病,2017,27(8):700-702.
[24]任强,付钰淋,李华,等.陕西省新发现艾滋病感染者HIV耐药警戒线调查研究[J].现代检验医学杂志,2017,32(6):136-138.
[25]邱月锋,张春阳,夏品苍,等.福建省2013年艾滋病病毒耐药警戒线调查[J].中国病毒病杂志,2016,6(4):275-278.
[26]杨蒙蒙.江苏省男男性行为人群HIV获得性和传播性耐药流行情况研究[D].南京：南京医科大学,2016.
[27]刘晓明,艾德尔艾力·阿有甫,张靖,等.新疆和田地区新近诊断HIV-1人群耐药传播及亚型分布情况调查.安徽预防医学杂志,2016,22(6):371-374.
[28]Zhao B,Han X,Dai D,et al.New trends of primary drug resistance among HIV type 1-infected men who have sex with men in Liaoning Province,China[J].AIDS Res Hum Retroviruses,2011,27(10):1047-53.
[29]Wang X,Wu Y,Mao L,et al.Targeting HIV Prevention Based on Molecular Epidemiology Among Deeply Sampled Subnetworks of Men Who Have Sex With Men[J].Clin Infect Dis,2015,61(9):1462-1468.
[30]Zhao S,Feng Y,Hu J,et al.Prevalence of Transmitted HIV drug resistance in antiretroviral treatment na?ve newly diagnosed individuals in China[J].Sci Rep,2018,8(1):12273.
[31]Lu X,Chen S,Zhao H,et al.Baseline Investigation of HIV-1 Primary Drug Resistance Among Newly Diagnosed Treatment-Na?ve HIV-1 Individuals in Hebei,China[J].AIDS Res Hum Retroviruses,2018,34(12):142.
[32]Wang X,Liu X,Li F,et al.Epidemiological surveillance of HIV-1 transmitted drug resistance among newly diagnosed individuals in Shijiazhuang,northern China,2014-2015[J].PLoS One,2018,13(6):e0198005.
[33]徐理倩,韩志刚,张亚丽,等.广州市2008-2015年未接受抗病毒治疗的注射吸毒人群HIV-1感染者耐药分析[J].中华流行病学杂志,2019,40(2):196-201.
[34]Stecher M,Chaillon A,Eis-Hübinger AM,et al.Pretreatment human immunodeficiency virus type 1(HIV-1)drug resistance in transmission clusters of the CologneBonn region,Germany[J].Clin Microbiol Infect,2019,25(2):253,e1-253.
[35]Ngo-Giang-Huong N,Huynh T,Dagnra AY,et al.Prevalence of pretreatment HIV drug resistance in West African and Southeast Asian countries[J].J Antimicrob Chemother2019,74(2):462-167.
[36]Chimukangara B,Kharsany A,Lessells RJ,et al.Moderateto-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province,South Africa[J].AIDS Res Hum Retroviruses,2019,35(2):129-38.
[37]Coelho L,Matsuda EM,Nogueira RS,et al.Prevalence of HIV-1 transmitted drug resistance and viral suppression among recently diagnosed adults in S?o Paulo,Brazil[J].Arch Virol,2019,164(3):699-706.
[38]Liu P,Liao L,Xu W,et al.Adherence,virological outcome,and drug resistance in Chinese HIV patients receiving first-line antiretroviral therapy from 2011 to2015[J].Medicine(Baltimore),2018,97(50):e13555.
[39]Lin B,Sun X,Su S,et al.HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province,China[J].PLoS One,2017,12(7):e0181997.
[40]Dong K,Ye L,Leng Y,et al.Prevalence of HIV-1 Drug Resistance among Patients with Antiretroviral Therapy Failure in Sichuan,China,2010-2016[J].Tohoku J Exp Med 2019,247(1):1-12.
[41]兰芸,蔡卫平,李凌华,等.2015年广东省抗病毒治疗失败艾滋病患者非核苷类逆转录酶抑制剂耐药相关基因突变分析[J].中华临床感染病杂志,2017,10(1):14-19.
[42]曹慜,杨东智,吴忠兰,等.宁夏抗病毒治疗患者HIV基因型耐药及亚型分析[J].现代预防医学,2018,45(1):149-154.
[43]卢静,徐晓琴,周莹,等.江苏省HIV-1基因型抗病毒治疗失败患者耐药检测结果分析[J].中国感染控制杂志,2018,17(10):884-888.
[44]周莹,卢静,张之,等.江苏省艾滋病一线药物抗病毒治疗失败病人的耐药特征及影响因素分析[J].中华疾病控制杂志,2017,21(12):1191-1194,1199.
[45]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.
[46]吴昊,高凯,张亚丽,等.广州市孕产妇人群HIV-1亚型分布和耐药特征分析[J].疾病监测,2018,33(11):913-918.
[47]Zhao Y,Mu W,Harwell J,et al.Drug resistance profiles among HIV-1-infected children experiencing delayed switch and 12-month efficacy after using second-line antiretroviral therapy:an observational cohort study in rural China[J].J Acquir Immune Defic Syndr,2011,58(1):47-53.
[2]Zhang F,Dou Z,Yu L,et al.The effect of highly active antiretroviral therapy on mortality among HIV-infected former plasma donors in China[J].Clin Infect Dis,2008,47(6):825-833.
[3]Zhang F,Dou Z,Ma Y,et al.Five-year outcomes of the China National Free Antiretroviral Treatment Program[J].Ann Intern Med,2009,151(4):241-251.
[4]Jia Z,Mao Y,Zhang F,et al.Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China(2003-11):a national observational cohort study[J].Lancet,2013,382(9899):1195-1203.
[5]B e n n e t t D E,M y a t t M,B e r t a g n o l i o S,e t a l.Recommendations for surveillance of transmitted HIVdrug resistance in countries scaling up antiretroviral treatment[J].Antivir Ther,2008,13(Suppl 2):25-36.
[6]Bennett DE,Bertagnolio S,Sutherland D,et al.The World Health Organization's global strategy for prevention and assessment of HIV drug resistance[J].Antivir Ther,2008,13(Suppl 2):1-13.
[7]Bennett DE,Camacho RJ,Otelea D,et al.Drug resistance mutations for surveillance of transmitted HIV-1 drugresistance:2009 update[J].PLoS One,2009,4(3):e4724.
[8]WHO.HIV drug resistance report 2017[EB/OL].http://www.who.int/hiv/pub/drugresistance/hivdr-report-2017/en/.
[9]徐军强,曹韵贞.HIV-1耐药性研究的新进展[J].国外医学（病毒学分册）,2001,8(5):158-161,封二.
[10]张旻,尚红,韩晓旭,等.中国东北地区未经抗病毒治疗的HIV/AIDS患者HIV毒株的耐药基因变异研究[J].中华微生物学和免疫学杂志,2004,24(11):850-854.
[11]司雪峰,黄海龙,魏民,等.我国HIV-1感染者耐药突变的流行性研究[J].中华实验和临床病毒学杂志,2004,18(4):308-311.
[12]Li JY,Li HP,Li L,et al.Prevalence and evolution of drug resistance HIV-1 variants in Henan,China[J].Cell Res,2005,15(1):843-849.
[13]Ma Y,Zhang F,Li H,et al.Monitoring HIV drug resistance using early warning indicators in China:results from a pilot survey conducted in 2008[J].Clin Infect Dis,2012,54(Suppl 4):S300-S302.
[14]Shafer RW,Rhee SY,Pillay D,et al.HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance[J].AIDS,2007,21(2):215-223.
[15]Jordan MR,Bennett DE,Bertagnolio S,et al.World Health Organization surveys to monitor HIV drug resistance prevention and associated factors in sentinel antiretroviral treatment sites[J].Antivir Ther,2008,13(Suppl 2):15-23.
[16]WHO.HIV Fact sheet.Updated July 2017[EB/OL].Avaliable at:http://www.who.int/mediacentre/factsheets/fs360/en/.
[17]吴亚松,马烨.HIV耐药评估和预防策略[J].传染病信息,2017,30(6):351-4.
[18]Liao L,Xing H,Dong Y,et al.Surveys of transmitted HIV drug resistance in 7 geographic Regions in China,2008-2009[J].Clin Infect Dis,2012,54(Suppl 4):S320-323..
[19]陈敏,王继宝,邢辉,等.云南省德宏傣族景颇族自治州2015年HIV-1耐药传播警戒线调查[J].中华流行病学杂志,2017,38(7):959-962.
[20]苏莹珍,贾曼红,杨颖,等.云南省昆明市2011年HIV-1耐药警戒线调查[J].现代预防医学,2014,41(6):1120-1122.
[21]陈敏,贾曼红,苏莹珍,等.云南省文山州2012年HIV-1基因型和耐药传播警戒线调查[J].中华疾病控制杂志,2013,17(12):1041-1045.
[22]孙晓光,于海英,苏生利,等.山东省2013-2015年新发现未治疗HIV-1感染者耐药毒株传播警戒线调查[J].中华预防医学杂志,2017,51(7):604-609.
[23]吴可可,苏德华,吴矛矛.温州地区未治疗AIDS病人的HIV毒株耐药基因变异研究[J].中国艾滋病性病,2017,27(8):700-702.
[24]任强,付钰淋,李华,等.陕西省新发现艾滋病感染者HIV耐药警戒线调查研究[J].现代检验医学杂志,2017,32(6):136-138.
[25]邱月锋,张春阳,夏品苍,等.福建省2013年艾滋病病毒耐药警戒线调查[J].中国病毒病杂志,2016,6(4):275-278.
[26]杨蒙蒙.江苏省男男性行为人群HIV获得性和传播性耐药流行情况研究[D].南京：南京医科大学,2016.
[27]刘晓明,艾德尔艾力·阿有甫,张靖,等.新疆和田地区新近诊断HIV-1人群耐药传播及亚型分布情况调查.安徽预防医学杂志,2016,22(6):371-374.
[28]Zhao B,Han X,Dai D,et al.New trends of primary drug resistance among HIV type 1-infected men who have sex with men in Liaoning Province,China[J].AIDS Res Hum Retroviruses,2011,27(10):1047-53.
[29]Wang X,Wu Y,Mao L,et al.Targeting HIV Prevention Based on Molecular Epidemiology Among Deeply Sampled Subnetworks of Men Who Have Sex With Men[J].Clin Infect Dis,2015,61(9):1462-1468.
[30]Zhao S,Feng Y,Hu J,et al.Prevalence of Transmitted HIV drug resistance in antiretroviral treatment na?ve newly diagnosed individuals in China[J].Sci Rep,2018,8(1):12273.
[31]Lu X,Chen S,Zhao H,et al.Baseline Investigation of HIV-1 Primary Drug Resistance Among Newly Diagnosed Treatment-Na?ve HIV-1 Individuals in Hebei,China[J].AIDS Res Hum Retroviruses,2018,34(12):142.
[32]Wang X,Liu X,Li F,et al.Epidemiological surveillance of HIV-1 transmitted drug resistance among newly diagnosed individuals in Shijiazhuang,northern China,2014-2015[J].PLoS One,2018,13(6):e0198005.
[33]徐理倩,韩志刚,张亚丽,等.广州市2008-2015年未接受抗病毒治疗的注射吸毒人群HIV-1感染者耐药分析[J].中华流行病学杂志,2019,40(2):196-201.
[34]Stecher M,Chaillon A,Eis-Hübinger AM,et al.Pretreatment human immunodeficiency virus type 1(HIV-1)drug resistance in transmission clusters of the CologneBonn region,Germany[J].Clin Microbiol Infect,2019,25(2):253,e1-253.
[35]Ngo-Giang-Huong N,Huynh T,Dagnra AY,et al.Prevalence of pretreatment HIV drug resistance in West African and Southeast Asian countries[J].J Antimicrob Chemother2019,74(2):462-167.
[36]Chimukangara B,Kharsany A,Lessells RJ,et al.Moderateto-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province,South Africa[J].AIDS Res Hum Retroviruses,2019,35(2):129-38.
[37]Coelho L,Matsuda EM,Nogueira RS,et al.Prevalence of HIV-1 transmitted drug resistance and viral suppression among recently diagnosed adults in S?o Paulo,Brazil[J].Arch Virol,2019,164(3):699-706.
[38]Liu P,Liao L,Xu W,et al.Adherence,virological outcome,and drug resistance in Chinese HIV patients receiving first-line antiretroviral therapy from 2011 to2015[J].Medicine(Baltimore),2018,97(50):e13555.
[39]Lin B,Sun X,Su S,et al.HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province,China[J].PLoS One,2017,12(7):e0181997.
[40]Dong K,Ye L,Leng Y,et al.Prevalence of HIV-1 Drug Resistance among Patients with Antiretroviral Therapy Failure in Sichuan,China,2010-2016[J].Tohoku J Exp Med 2019,247(1):1-12.
[41]兰芸,蔡卫平,李凌华,等.2015年广东省抗病毒治疗失败艾滋病患者非核苷类逆转录酶抑制剂耐药相关基因突变分析[J].中华临床感染病杂志,2017,10(1):14-19.
[42]曹慜,杨东智,吴忠兰,等.宁夏抗病毒治疗患者HIV基因型耐药及亚型分析[J].现代预防医学,2018,45(1):149-154.
[43]卢静,徐晓琴,周莹,等.江苏省HIV-1基因型抗病毒治疗失败患者耐药检测结果分析[J].中国感染控制杂志,2018,17(10):884-888.
[44]周莹,卢静,张之,等.江苏省艾滋病一线药物抗病毒治疗失败病人的耐药特征及影响因素分析[J].中华疾病控制杂志,2017,21(12):1191-1194,1199.
[45]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.
[46]吴昊,高凯,张亚丽,等.广州市孕产妇人群HIV-1亚型分布和耐药特征分析[J].疾病监测,2018,33(11):913-918.
[47]Zhao Y,Mu W,Harwell J,et al.Drug resistance profiles among HIV-1-infected children experiencing delayed switch and 12-month efficacy after using second-line antiretroviral therapy:an observational cohort study in rural China[J].J Acquir Immune Defic Syndr,2011,58(1):47-53.