HIV-1N348I耐药突变流行状况及突变模式的研究

李韩平; 韩扬; 朱新鹏; 路新利; 郭伟; 刘永健; 鲍作义; 李林; 庄道民; 刘思扬; 李敬云

Abstract

李韩平,韩扬,朱新鹏,路新利,郭伟,刘永健,鲍作义,李林,庄道民,刘思扬,李敬云.HIV-1N348I耐药突变流行状况及突变模式的研究[J].Chinese journal of Epidemiology,2011,32(9):908-912

HIV-1N348I耐药突变流行状况及突变模式的研究

Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1

Received:April 02, 2011

DOI：

KeyWord: 艾滋病毒1型耐药 N348I

English Key Word: HIV-1 Resistance N348I

FundProject:国家自然科学基金（30800938,30830088）：国家“十一五”科技重大专项（2008ZX10001-004）

Author Name	Affiliation	E-mail
LI Han-ping	The State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, China
HAN Yang	Peking Union Medical College Hospital
ZHU Xin-peng	Henan Provincial Center for Disease Control and Prevention
LU Xin-li	Hebei Provincial Center for Disease Control and Prevention
GUO Wei	The State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, China
LIU Yong-jian	The State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, China
BAO Zuo-yi	The State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, China
LI Lin	The State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, China
ZHUANG Dao-min	The State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, China
LIU Si-yang	The State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, China
LI Jing-yun	The State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, China	lijy@nic.bmi.an.cn

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Abstract:

目的阐明HIV-1耐药相关突变N348I在中国艾滋病患者中的流行率及突变模式。方法用RT-PCR从血浆标本中扩增614例治疗失败和619例未治疗的艾滋病患者的HIV-1 pol基因蛋白酶(PR)反转录酶(RT)全长基因(2100 bp)。将获得的1233条序列提交斯坦福大学HIV-1耐药数据库，根据数据库比对结果，分析N348I出现的频率及模式。结果N348I突变在抗病毒治疗失败患者中的流行率为6.5％,在未治疗患者中的流行率为0.8％。使用含齐多夫定(AZT)方案治疗的患者，N348I突变的流行率显著高于使用不含AZT方案治疗的患者(14.1％ vs.4.7％，x2=10.21,P＜0.01)；在出现N348I突变的接受治疗的患者中，N3481均以与其他突变联合的形式出现，与胸苷类似物耐药突变(TAMs)共同发生占85.0％(34/40)、与M184V/I共同出现占52.5％。结论使用一线方案治疗失败的艾滋病患者中，N348I突变有一定流行，该突变的发生以特有突变模式出现。

English Abstract:

Objective To elucidate the prevalence and the mutation pattern of N348I that related to the resistance seen in the AIDS patients, in China. Methods Partial pol gene of HIV-1 comprising of full protease (PR) and reverse transeriptase (RT) was obtained from plasma samples of therapy-failure individuals (n=614) and therapy-naive individuals (n=619) by using reverse transcription polymerase chain reaction(RT-PCR). 1233 sequences were then submitted to the HIV-1 drug resistance database of the Stanford University to analyze the prevalence and the emergence pattern of N348I.Results The prevalence of N348I was 6.5％ in the therapy-failure patients and 0.8％ in the naive individuals, respectively. The prevalence of N348I was more popular among those patients whose ART regimens containing zidovudine (AZT or ZDV) than those without AZT in regimens( 14.1％ vs. 4.7％, x2=10.21, P＜0.01 ). N3481 always emerged, and combined with others mutations among patients of ART, whose frequencies were: 85.0％ in combination with thymidine analog mutations (TAMs) and 52.5％ with M184V/I, respectively. Conclusion N348I was somehow prevalent in the therapy-failure patients when using the first-line antiretroviral drugs,and it emerged as unique patterns. This study laid the ground in improving the techaology of drug resistance genotypes detection and providing theoretical basis to study the mechanism of resistance and the law of molecular evolution.

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