湖北省抗病毒治疗和未治疗的HIV-1感染者耐药基因变异研究

王晓琼; 童骁; 汤恒; 刘萍萍; 张伟; 杨荣阁

Abstract

王晓琼,童骁,汤恒,刘萍萍,张伟,杨荣阁.湖北省抗病毒治疗和未治疗的HIV-1感染者耐药基因变异研究[J].Chinese journal of Epidemiology,2007,28(11):1112-1115

湖北省抗病毒治疗和未治疗的HIV-1感染者耐药基因变异研究

Study on gnotypic resistance mutations to antiretroviral drugs on HIV strains of treated and treatment-naive HIV·1 infectious patients in Hubei province

Received:June 28, 2007

DOI：

KeyWord: 艾滋病病毒耐药变异高效抗逆转录病毒治疗

English Key Word: HIV Drug resistance mutations Highly active antiretroviral therapy

FundProject:国家“973计划”资助项目(2005cB522903)；国家“863计划”资助项目(2005AA219070)

Author Name	Affiliation	E-mail
WANG Xiao-qiong	HIV Molecular Biology Laboratory, The State Key Laboratory of Virology, Wuhan Institution of Virology, Chinese Academy of Science, Wuhan 430071 China
TONG Xiao	HIV Molecular Biology Laboratory, The State Key Laboratory of Virology, Wuhan Institution of Virology, Chinese Academy of Science, Wuhan 430071 China
TANG Heng	湖北省疾病预防控制中心性病艾滋病防治所
LIU Ping-ping	HIV Molecular Biology Laboratory, The State Key Laboratory of Virology, Wuhan Institution of Virology, Chinese Academy of Science, Wuhan 430071 China
ZHANG Wei	HIV Molecular Biology Laboratory, The State Key Laboratory of Virology, Wuhan Institution of Virology, Chinese Academy of Science, Wuhan 430071 China
YANG Rong-ge	HIV Molecular Biology Laboratory, The State Key Laboratory of Virology, Wuhan Institution of Virology, Chinese Academy of Science, Wuhan 430071 China	ryang@wh.iov.cn

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Abstract:

目的研究湖北省流行的HIV一1毒株在经过高效抗逆转录病毒治疗(HAART)及未治疗人群中耐药基因变异情况。方法采集HIV一1感染者抗凝外周血，提取前病毒DNA，用巢式PcR方法扩增HIv-1声o￡基因约2 kb的核酸序列，进行序列测定并通过斯坦福耐药基因数据库进行耐药基因型分析。结果抗病毒治疗组19例，未治疗组25例。在所有的HIV一1感染者样本序列中，发现针对蛋白酶抑制剂(PIs)的耐药突变：D30N(2.27％)，D30G(2.27％)，M46I(4.55％)，M46N(2.27％)，147v(4.55％).184v(4.55％)，184L(2.27％)，N88S(2.27％)，L90S(2.27％)，以及针对PIs的次要耐药基因突变；A71T(29.55％)。在治疗组中出现针对逆转录酶抑制剂(NRTIs及NNRTIs)的主要耐药基因突变的样本5例，突变主要有M41L(5.26％)，A62V(5.26％)，D67N(5.26％)，L210w(5.26％)，T215Y(15.79％)；K103E(5.26％)，K103N(10.53％)，Y181C(5.26％)，G190A(5.26％)，K238N(5.26％)。在未治疗组中出现针对逆转录酶抑制剂(NRTIs及NNRTIs)的主要耐药基因突变的样本5例，突变主要有M184V(4％)，K65N(4％)，Y115M(4％)，F116L(4％)，M184I(4％)；V179D(4％)，G190R(4％)。在逆转录酶(RT)基因中耐药意义不明的突变F214L，与药物的使用有统计学上的相关性(P=O.03)。结论湖北省HIv一1感染者RT基因的耐药突变，在治疗和未治疗人群样本中差异有统计学意义，说明药物治疗已经对HIV耐药基因突变的产生有了一定影响。同时，耐药意义尚未明确的突变位点F214L也可能与治疗或是某些药物的使用有一定的相关性。

English Abstract:

objective To study the drug resistance status on HIV一1 patients who had been treatedwith highly active antiretroviral therapy(HAART)and those treatment-naive ones in Hubei province.methods Nested polymerase chain reaction(PCR)was used to amplifv 2 kb DNA fragment in HIV声oZgene from peripheral blood of the HIV infected patients and the PCR products were sequenced. Thesequences were compared to the StanfOrd HIV drug resistance database. results Nineteen patients weretreated with regimens composed of two Nucleoside Reverse Transc“ptase Inhibitors(NRTIs)and one Non-NucleOside Reverse Transcriptase Inhibjtors(NNRTI)，with 25 patients as treatment-naive.Some protease(PR)drug_resistant mutations were found in these samples，such as D30N(2.27％)，D30G(2.27％)，M46I(4.55％)，M46N(2.27％)，147V(4.55％)，184V(4.55％)，184L(2.27％)，N88S(2.27％)andL90S(2.27％)that all belonged to major drug+resistant but A71T(29.55％)belonged to minor resistancemutations Five treated patients were detected having mutations associated RT drug resistance： M41L(5.26％)，A62V(5.26％)，D67N(5.26％)，L210w(5.26％)，T215Y(15.79％)；K103E(5.26％)，K103N(10.53％)，Y181C(5.26％)，G190A(5.26％)，K238N(5.26％)，while five treatment-naivepatients were detected to have had mutations associated RT drug resistance M184V(4％)，K65N(4％)，Y115M(4％)，F116L(4％)，M184I(4％)，V179D(4％)，G190R(4％).Some additional mutations were detected in RT whose mle inv01ve in drug resistance still remained unknown. F214L was positivelyassociated with HAART treatment(PCR0.03).conclusion Significant differences were found betweendrug resistance mutations to RTIs in treated and treat-naTve patients in Hubei province，indicating that drugshad affected the occurrence of drug resistance mutations. At the same time，novel RT mutations F2 1 4Lmight be associated with HAART or some other drugs.

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