贵州省治疗病人hiv-1耐药基因突变研究

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1、《中国图书资料分类法》单位代码：10660分类号：R392.12学号：TS100144贵阳医学院2013届硕士学位论文贵州省治疗病人HIV-1耐药基因突变研究研究生：卜朴导师：左丽教授年级：2010级专业：免疫学2013年5月28日目录中文摘要„„„„„„„„„„„„„„„„„„„„„„01前言„„„„„„„„„„„„„„„„„„„„„„„„03材料与方法„„„„„„„„„„„„„„„„„„„„„05结果„„„„„„„„„„„„„„„„„„„„„„„„13讨论„„„„„„„„„„„„„„„„„„„„„„„„24结论„„„„„„„„„„„

2、„„„„„„„„„„„„„28参考文献„„„„„„„„„„„„„„„„„„„„„„29英文摘要„„„„„„„„„„„„„„„„„„„„„„32致谢„„„„„„„„„„„„„„„„„„„„„„„„33中英文对照词缩略表„„„„„„„„„„„„„„„„„34论文版权使用授权书和独创性声明„„„„„„„„„„„35附：综述„„„„„„„„„„„„„„„„„„„„„„37贵阳医学院2013届硕士论文中文摘要贵州省治疗病人HIV-1耐药基因突变研究专业：免疫学研究生卜朴导师左丽教授摘要目的:研究贵州省经抗逆转录病毒治疗的艾滋病感染者/艾滋病病人（

3、HIV/AIDS）的人免疫缺陷病毒(HumanImmunodeficiencyvirus，HIV)的蛋白酶区和逆转录酶区耐药基因变异情况，为更有效的开展高效抗逆转录病毒治疗提供参考依据。方法：采集贵州省抗病毒治疗的感染者/艾滋病病人（HIV/AIDS）56例的血样，进行RNA核酸提取、采用套式逆转录-聚合酶链反应(ReverseTranscription-PolymeraseChainReaction，RT-PCR)扩增HIV-1pol基因片段及基因测序，对所得结果登录美国斯坦福大学HIV耐药数据库进行在线分析确定耐药突变情况。结果:分

4、析获得的44例目的基因片段，亚型分布为：AE亚型17例、BC亚型15例、C亚型10例及2例B亚型。26例发生基因突变,逆转录酶抑制剂（reversetranscriptaseinhibitors，RTIs）突变率和蛋白酶抑制剂(proteaseinhibitors，PIs)突变率分别为45.5%（20/44）和13.6%（6/44）,其中核苷酸类逆转录酶抑制剂（nucleotidereversetranscriptaseinhibitors，NRTIs）耐药突变发生率为34.1%（15/44）,非核苷类逆转录酶抑制剂(non-Nucle

5、osidereversetranscriptaseinhibitors，NNRTIs)耐药突变发生率38.6%（17/44）。发现了胸腺嘧啶类似物(ThymLdineAnalogMutations,TAMs)耐药突变（D67N，T215NSTY，K70KR，K219EK）。耐药分析结果显示：出现了对核苷类转录酶抑制剂药物拉米夫定(lamLvudine，3TC)、阿巴卡韦（Abacavir，ABC)、齐多夫定(Zidovudine，AZT)、司他夫定(Dtavudine，D4T)、去羟肌苷(Didanosine，ddI)、替若福韦(Ten

6、ofovir，TDF)、恩曲他宾（Emtricitabine，FTC)和非核苷类逆转录酶抑制剂药物奈韦拉平(Nevirapine，NVP)、依曲韦林(Etravirine，ETR)、依法韦伦(Efavirenz，EFV)、利匹韦林(Rilpivirine，RPV)的耐药毒株，发现1例对蛋白酶抑制剂奈非那韦（Nelfinavir，NFV）低度耐药的毒株。1贵阳医学院2013届硕士论文中文摘要结论:1.NRTIs与NNRTIs均发现耐药毒株,而PIs发现1例低度耐药毒株，显示对NRTIs和NNRTIs均耐药的毒株有可能对PIs类敏感，提示对

7、NRTIs和NNRTIs治疗失败的病人，可选择PIs类药物作为替换药物进行治疗。2．在应用NNRTIs治疗后，K103N、Y181C、G19OA耐药位点变异频率高，单一位点变异即可引起所有NNRTIs的多药耐药。应用NRTIs治疗后，M184V位点发生突变的几率最高。[关键词]HIV-1，耐药突变，蛋白酶基因，逆转录酶基因2贵阳医学院2013届硕士论文前言前言自1981年获得性免疫缺陷综合征(AcquiredImmunodeficiencySyndrome，AIDS)被人们认识以来，AIDS的流行呈上升趋势，AIDS是由人类免疫缺陷病毒

8、+（HumanImmunodeficiencyVirus，HIV）感染引起的，以人体CD4T淋巴细胞减少为特征的进行性免疫功能缺陷，继发各种机会性感染、恶性肿瘤和中枢神经[1,2]系统病变的综合性疾患。20