温州地区HIV/AIDS病人抗病毒治疗后耐药基因变异研究

Research of HIV-1 drug resistance mutations in Wenzhou area

目的通过调查分析温州地区已接受抗病毒治疗病人体内艾滋病病毒（HIV）毒株的耐药基因的突变发生率,为采取相应防治措施提供可靠的依据,同时指导抗病毒药物的使用。方法收集温州的11个县市区在2010-2015年接受抗病毒治疗的HIV感染者/艾滋病（AIDS）病人625例,病毒载量大于1 000拷贝/mL的70例,进行HIV蛋白酶（PR）全长和部分反转录酶（RT）基因的扩增、脱氧核糖核酸（DNA）测序、亚型鉴定,并与国际HIV耐药数据库比对分析。结果在68例获得有效序列患者中,其中亚型分布显示,CRF01_AE占52.94%（36/68）,B亚型占17.65%（12/68）,BC重组占25.00%（17/68）,C亚型占4.41%（3/68）。抗病毒治疗患者对蛋白酶抑制剂（PI）、核苷类反转录酶抑制剂（NRTI）和非核苷类反转录酶抑制剂（NNRTI）的耐药率,分别为0.48%（3/625）,7.84%（49/625）和8.32%（52/625）,总耐药率为8.80%（55/625）。NRTI主要突变位点为M184V,NNRTI主要突变位点为Y181C。结论通过对抗病毒治疗病人调查发现,温州总体耐药率处于较低水平。M184V、Y181C突变位点检出率高,耐药的严重程度依次为NNRTIs〉NRTIs〉PIs。应结合实际,科学合理用药。

Objective To investigate and analyze the incidence of HIV strains resistant gene mutation to further guide the proper regimens of antiviral drugs.Methods Information of 625 AIDS patients receiving antiretroviral therapy were collected,and RT-PCR was used to amplify the whole protease（PR）and part of reverse transcriptase（RT）gene.The drug resistance results were compared with those in the international HIV drug resistance database.Results A total of 68 fragments were obtained from the cases,in which 36 was CRF01_AE（52.94%）,12 B（17.64%）,17 subtype BC（25.00%）,and 3 subtype C（4.41%）.The drug resistance rate for protease inhibitors（PI）,nucleoside reverse transcriptase inhibitors（NRTI）and non-nucleoside reverse transcriptase inhibitor（NNRTI）was 0.48%（3/625）,7.84%（49/625）,and 8.32%（52/625）.The total drug resistance rate was 8.80%（55/625）.The main site of NRTI mutations lay in M184 V,and the main site of NNRTI mutation was Y181 C.Conclusion For the antiviral treatment group,HIV drug resistance is at a low level.The detection rates of M184 Vand Y181 Cmutation site are high,and the severity of drug resistance were NNRTIs〉NRTIs〉PIs.