我国6个省19个城市男男性行为人群HIV-1基因亚型及抗病毒治疗前耐药分析

Analysis of HIV-1 genetic subtype and pretreatment drug resistance among men who have sex with men infected with HIV-1 from 19 cities of 6 provinces in China

目的分析我国6个省19个城市男男性行为人群(MSM)HIV-1基因亚型分布及抗病毒治疗前耐药情况。方法2019年4-11月,在河北、山东、江苏、浙江、福建和广东6个省19个城市收集未接受抗病毒治疗MSM HIV-1感染者的血浆样本574份,提取RNA,反转录后经巢式PCR扩增HIV-1 pol基因区片段。PCR产物测序后进行序列分析,构建系统进化树判定病毒基因亚型,提交斯坦福耐药数据库分析耐药。结果有479份样本PCR扩增成功并获得核酸序列,检出的HIV-1基因亚型有9种,其中CRF01_AE(43.4%)和CRF07_BC(36.3%)所占比例较大,随后依次为B(6.3%)、CRF55_01B(5.9%)、CRF59_01B(0.8%)、CRF65_cpx(0.8%)、CRF103_01B(0.4%)、CRF67_01B(0.4%)和CRF68_01B(0.2%);另有26份(5.5%)样本的基因亚型为未知亚型。不同省份之间的基因亚型构成比差异有统计学意义(χ^(2)=44.141,P<0.001)。总体抗病毒治疗前耐药率为4.6%(22/479),其中对非核苷类反转录酶抑制剂、核苷类反转录酶抑制剂和蛋白酶抑制剂的耐药率分别为3.5%(17/479)、0.8%(4/479)和0.2%(1/479)。新近感染者的抗病毒治疗前耐药率高于长期感染者,差异有统计学意义(χ^(2)=4.634,P=0.031)。结论我国6个省19个城市MSM的HIV-1感染者中HIV-1基因亚型多样化,不同省份之间的基因亚型构成比不同;整体抗病毒治疗前耐药率处于低水平,但新近感染者的耐药率较高,建议重点加强此类人群的耐药监测。

Objective To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance(PDR)among men who have sex with men(MSM)from 19 cities of 6 provinces in China.Methods From April to November 2019,574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei,Shandong,Jiangsu,Zhejiang,Fujian,and Guangdong provinces,total ribonucleic acid(RNA)was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction(PCR)after reverse transcription.Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis.Results A total of 479 samples were successfully amplified by PCR.The HIV-1 genetic subtypes included CRF01_AE,CRF07_BC,B,CRF55_01B,CRF59_01B,CRF65_cpx,CRF103_01B,CRF67_01B,CRF68_01B and unrecognized subtype,which accounted for 43.4%,36.3%,6.3%,5.9%,0.8%,0.8%,0.4%,0.4%,0.2%and 5.5%,respectively.The distribution of genetic subtypes among provinces is statistically different(χ^(2)=44.141,P<0.001).The overall PDR rate was 4.6%(22/479),the drug resistance rate of non-nucleoside reverse transcriptase inhibitors,nucleoside reverse transcriptase inhibitors,and protease inhibitors were 3.5%(17/479),0.8%(4/479)and 0.2%(1/479),respectively.The PDR rate of recent infections was significantly higher than that of long-term infections(χ^(2)=4.634,P=0.031).Conclusions The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse,and the distribution of subtypes is different among provinces.The overall PDR rate is low,while the PDR rate of recent infections was significantly higher than that of long-term infections,suggesting the surveillance of PDR in recent infections should be strengthened.