四川地区HIV/AIDS患者基因亚型及传播性耐药现状研究

Genetic Subtypes and Status of Transmitted Drug Resistance of HIV/AIDS Patients in Sichuan

目的分析四川地区初治HIV/AIDS患者的HIV基因亚型分布特点和传播性耐药现状。方法纳入四川地区住院且无抗反转录病毒治疗(ART)药物暴露史的成年HIV/AIDS患者,采用In-house测序法进行HIV基因测序,系统进化树判定HIV基因亚型,美国斯坦福大学HIV耐药数据库在线比对耐药突变位点并确定是否存在耐药及耐药种类、耐药水平。结果共纳入符合标准的120例患者,采集120份血液样本。87.5%样本HIV基因扩增成功(105/120),HIV基因亚型分布特点:CRF01_AE占比46.67%(49/105),CRF07_BC占比39.05%(41/105),其他占比14.28%(15/105)。不同性别、年龄、民族、感染途径、耐药、HIVRNA水平、CD4水平等基因亚型的差异均无统计学意义(P>0.05)。25份样本检测到耐药突变位点(20.83%),20份样本潜在耐药(16.67%),5份样本传播性耐药(4.17%)。24份样本对非核苷类反转录酶抑制剂(NNRTIs)耐药,V179D/E位点突变频率最高,1份样本对蛋白酶抑制剂耐药,突变位点M46I,未发现核苷类反转录酶抑制剂耐药及整合酶抑制剂耐药。结论四川地区初治住院成年HIV/AIDS患者HIV基因亚型分布特点以CRF01_AE和CRF07_BC为主,传播性耐药率较低,以NNRTIs耐药为主。进行HIV基线耐药检测对制定有效ART方案具有重要意义。

Objective To investigate the distribution characteristics of the HIV genetic subtypes and the status quo of transmitted drug resistance among HIV/AIDS patients in Sichuan with no previous history of receiving antiretroviral therapy(ART).Methods Adult HIV/AIDS patients who were hospitalized in Sichuan and who had no previous history of exposure to ART drugs exposure were enrolled.In-house sequencing of the HIV gene was done and phylogenetic tree was constructed to analyze the HIV genetic subtypes.The Stanford HIV drug resistance database was used to make online comparison of the drug resistance mutation sites and to determine the presence or absence of drug resistance,and the type and level of drug resistance.Results A total of 120 patients were enrolled for the study,and 120blood samples were collected.The genetic subtypes of 87.5%(105/120)of the samples were successfully amplified.The distribution characteristics of HIV genotype were as follows,CRF01_AE accounted for 46.67%(49/105),CRF07_BC accounted for 39.05%(41/105),and the others genetic subtypes,14.28%(15/105).There were no significant differences between the different genetic subtypes in sex,age,ethnicity,HIV transmission route,drug resistance,baseline HIV RNA and baseline CD4(P>0.05).Drug-resistant mutation sites were detected in 25 samples,accounting for 20.83%(25/120)of all samples,with 16.67%(20/120)being potential drug resistance and 4.17%(5/120)being transmitted drug resistance.For the 24 samples found to be resistant to non-nucleoside reverse transcriptase inhibitors(NNRTIs),the mutation frequency of V179D/E was the highest.One patient showed resistance to protease inhibitors(PI)and the mutation site was M46I.No nucleoside reverse transcriptase inhibitor(NRTI)or integrase inhibitors(INTI)resistance were found.Conclusions The main genetic subtypes of HIV/AIDS patients in Sichuan with no previous history of receiving ART were CRF01_AE and CRF07_BC.The incidence of transmitted drug resistance was low.The drug resistance detected in the study was predominantly resistance to NNRTIs.Baseline HIV drug resistance testing is of great significance for formulating effective ART regimens.