河南省45例未经治疗的艾滋病患者蛋白酶和逆转录酶基因型耐药性检测与系统发生分析

杨坤; 李敬云; 鲍作义; 李韩平; 李林; 庄道民; 王哲; 李宏

Abstract

杨坤,李敬云,鲍作义,李韩平,李林,庄道民,王哲,李宏.河南省45例未经治疗的艾滋病患者蛋白酶和逆转录酶基因型耐药性检测与系统发生分析[J].Chinese journal of Epidemiology,2005,26(5):351-355

河南省45例未经治疗的艾滋病患者蛋白酶和逆转录酶基因型耐药性检测与系统发生分析

Genotypic antiretroviral resistance testing and phylogenetic analysis of protease and reverse transcriptase in antiretroviral drug-nave AIDS patients in Henan province

Received:July 10, 2004

DOI：

KeyWord: 艾滋病病毒序列分析基因型耐药性

English Key Word: Human immunodeficiency virus Sequence analysis Genotypic antiretroviral resistance

FundProject:卫生部艾滋病防治应用性研究基金资助项目(WA2003-02)

Author Name	Affiliation
YANG Kun	Insitute of Microbiology and Epidemiology, Beijing 100071, China
LI Jing-yun	Insitute of Microbiology and Epidemiology, Beijing 100071, China
BAO Zuo-yi	Insitute of Microbiology and Epidemiology, Beijing 100071, China
LI Han-ping	Insitute of Microbiology and Epidemiology, Beijing 100071, China
LI Lin	Insitute of Microbiology and Epidemiology, Beijing 100071, China
ZHUANG Dao-min	Insitute of Microbiology and Epidemiology, Beijing 100071, China
WANG Zhe	河南省疾病预防控制中心
LI Hong	河南省疾病预防控制中心

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Abstract:

目的了解河南省部分未经抗病毒治疗的艾滋病患者蛋白酶和逆转录酶基因耐药性突变发生的频率、类型和临床意义以及系统发生情况. 方法采集河南省45例未经抗病毒治疗的艾滋病患者的抗凝全血, 分离血浆, 用逆转录聚合酶链反应扩增pol区蛋白酶基因全序列与逆转录酶基因部分序列并直接进行序列测定, 提交Web站点http://hivdb. stanford. edu分析耐药性突变. 用BioEdit和DNAClub软件以及登陆Web站点http://hivweb. lanl. gov进行系统发生分析. 结果从36份血浆标本中扩增出pol区基因并进行了序列测定. 蛋白酶基因耐药性主要突变的发生率是8. 3%(3/36), 突变的类型是D30A、V32A、G73C和V82A;次要突变的发生率是100%, 突变的类型为L63PS(36/36)、I93L(35/36)、V77IL(34/36)、A71IVT(10/36)和D60E(2/36). 逆转录酶基因耐药性突变的发生率是38. 9%(14/36). 通过对耐药性突变进行评分, 并依据此分值解释其临床意义, 提示蛋白酶耐药率为5. 6%(2/36), 逆转录酶耐药率为22. 2%(8/36);另有1份标本对全部蛋白酶抑制剂、3份对部分逆转录酶抑制剂潜在低度耐药. 系统发生分析显示36份标本的pol区基因与B. US. 83. RFACCM17451的亲缘关系最为接近, 且彼此之间具有高度同源性, 推测此36份标本为同一感染来源, 其耐药性突变的发生不是源于耐药株感染, 而是病毒在体内进化的结果.结论河南省未经抗病毒治疗的艾滋病患者多数对现有的抗病毒药物敏感, 但抗病毒治疗必须遵守严格的程序并保持较好的依从性, 否则极易导致耐药性毒株的流行.

English Abstract:

Objective Frequency,type and clinical implications on protease and reverse transcriptase drug resistance mutations were investigated and phylogenetic analysis in antiretroviral drug-nave AIDS patients was carried out in Henan province. Methods 45 plasma samples were separated from the anticoagulatory whole blood,from which reverse transcription-polymerase chain reaction technique was used to amplify the partial pol gene. The sequences were analysed for genotypic antiretroviral resistance and phylogenetic relation through landing the websites http://hivdb.stanford.edu and http://hiv-web.lanl.gov,under BioEdit and DNAClub software. Results Partial pol sequences of 36 samples were successfully amplified. The major mutation rate of resistance to protease was 8.3 %(3/36),including types D30A,V32A,G73C and V82A. Minor mutation rate of resistance was 100%,including types of L63PS(36/36),I93L(35/36),V77IL(34/36),A71IVT(10/36)and D60E(2/36). The mutation rate of resistance to reverse transcriptase was 38.9 %(14/36). Mutation-scoring and clinical implication clewed drug resistance rates were 5.6 %(2/36)and 22.2 %(8/36)to protease inhibitors and reverse transcriptase inhibitors respectively,while 1 sample was potentially low-level resistant to all of the protease inhibitors and 3 samples to part of the reverse transcriptase inhibitors. Phylogenetic analysis revealed that the pol gene of 36 samples were highly homologous and having a near relative to B.US.83.RF ACC M17451. 36 samples seemed to have the same infection source while their resistance mutations were not due to drug-resistant virus infection but to the evolving of virus in vivo. Conclusion Most of the antiretroviral drug-nave AIDS patients in Henan province were sensitive to the currently available antiviral medicine,but antiviral treatment must be in accordance with the strict procedure and to keep better adherence, to avoid the epidemics caused by drug-resistant virus.

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