贵州省艾滋病患者耐药基因突变研究

Drug Resistance Gene Mutation in AIDS Patients in Guizhou Province

目的研究艾滋病(AIDS)患者耐药基因突变情况,为防止AIDS耐药传播及流行提供科学依据。方法采用NueliSens EasyQ荧光实时定量PCR系统对治疗1年以上的AIDS患者进行病毒载量检测,病毒载量>1 000 U/ml者采用Abbott公司ViroSeqTMHIV-1 Genotyping System V2.0系统进行扩增、测序和基因突变分析。结果 1 088例AIDS患者中病毒载量>1 000 U/ml者45例,获得POL区基因序列30例,且均有不同程度基因突变,仅7例产生耐药,总耐药率为0.64%(7/1 088);发现交叉耐药2例。7例耐药的AIDS患者均出现至少1种耐药相关基因突变位点,突变率为23.3%(7/30)。7例AIDS患者均对非核苷类逆转录酶抑制剂产生耐药基因突变,其耐药突变位点为K103N 4例、G190A 2例、V179D 1例、Y181C 1例、K101E 1例、M230L 1例,临床主要表现为对地拉韦定、依非韦仑及奈韦拉平高度耐药,其中有2例对核苷类逆转录酶抑制剂产生耐药基因突变,突变位点为M184V,临床上表现为对拉米夫定和恩曲他滨高度耐药。未见蛋白酶抑制剂耐药基因突变。结论贵州省AIDS患者的耐药情况目前仍处于较低水平且耐药形式较为单一;核苷类逆转录酶抑制剂及非核苷类逆转录酶抑制剂对贵州省AIDS患者的广泛治疗和使用仍然有效;及时监控和掌握AIDS患者的耐药基因突变情况,对于指导临床用药尤为重要。

Objectives To study drug resistance gene mutation in AIDS patients, to provide scientific base for pre- vention of the spreading and prevalence of AIDS drug resistance. Methods Bio - Maria NueliSens EasyQ fluorescence real - time quantitative PCR system was used to determine viral load in AIDS patients treated over 1 year. An analysis of amplification, sequencing and gene mutation was performed, by ViroSeqTMHIV - 1 Genotyping System V2.0 system made by Abbott, in pa- tients with viral load 〉 1 000 U/ml. Results In 1 088 AIDS patients, Viral load was 〉 1 000 U/m in 45, 30 gained valid gene sequence of POL with varying degrees of gene mutations, only 7 had drug resistance, the total drug resistance rate being 0.64% ; 2 cases had cross resistance. More than one kind of drug - resistance related gene mutable point were noted in the 7 pa- tients with drug resistance, with a mutable rate of 23.3% （7/30）. AIDS patients had drug resistance gene mutation to non - nucleoside reverse transcriptase inhibitor （ non - NRTI）, and its mutable points were K103N （4 cases）, G190A （2 cases）, VI79D （1 case）, Y181C （1 case）, K101E （1 case）, M230L （1 case）, clinically highly resistant to DLV, EFV, NVP. Two patients had drug resistance gene mutation to non - NRTI, MI84V being mutable point and clinically highly resistant to telbi- vudine and emtricitabine. Drug resistance gene mutation to proteinase inhibitors was not noted. Conclusions Situation of drug resistance is at a low level with relatively simple drug resistance form. NRTI and non - NRTI is still effective in antiviral treatment of AIDS in Guizhou Province. Timely monitoring and grasp of drug resistance gene mutation of AIDS patients are important to guidance to clinical medication.