绍兴市新确证HIV-1感染者分子传播网络及耐药基因分析

Molecular transmission network and drug resistance in newly reported HIV-1 cases in Shaoxing City,Zhejiang Province

目的 通过HIV毒株基因序列构建监测绍兴市新确证感染者传播关系的分子网络,分析网络特征为疫情流行趋势和防治提供依据。方法 分析2021年10月至2022年9月绍兴市新确认未经ART的249例感染者样本,采用RT-PCR和nest-PCR方法扩增HIV-1的pol基因,构建系统进化树分析亚型和不同基因距离的分子网络,通过美国斯坦福大学HIV耐药数据库HIVdb Program在线软件工具分析耐药突变位点。结果 获得186例样本序列,发现6种亚型,分别为CRF07_BC(96例,51.6%)、CRF01_AE(58例,31.2%)、CRF08_BC(22例,11.8%)、CRF85_BC(2例,1.1%)、CRF55_01B(5例,2.7%),以及独特重组型(CRF01_AE/CRF07_BC,3例,1.6%)。在0.75%为基因阈值,共形成20个分子簇,55条序列入网,入网率为29.6%(55/186),最大的分子簇C1包含13例病例,12例均为50岁以上人群,10例(76.9%)携带NNRTI耐药突变K103 N。C2分子簇为4例学生,均通过男男性行为途径感染。25例存在导致耐药的突变,治疗前耐药率为13.4%(25/186),其中NRTI耐药突变4例,分别为T69D、T215S/TA和L74I,NNRTI耐药突变21例分别为K103 N、E138A/EV/G、P225PH和Y188F,PI耐药突变4例,分别为L90LM、M46I、K20KT和N88 ND。结论 CRF07_BC亚型通过高危人群持续传播;50岁以上有推断的传播关系的老年人簇与MSM感染簇是绍兴市需要干预的重点目标,需要更有效的干预以防止病毒传播。

Objective Based on gene sequences of HIV strains,the molecular transmission network of newly diagnosed HIV infected individuals was constructed in Shaoxing City,Zhejian Province.Methods Plasma specimens from 249 antiretroviral-naive HIV cases were collected from October 2021 to September 2022.RT-PCR and nested PCR were used to amplify the pol gene of HIV-1,and phylogenetic tree was constructed to analyze the subtypes and molecular network with different gene distances.Drug resistant mutation sites were analyzed via the HIVdb Program online software from Stanford University HIV Drug Resistance Database of the United States.Results The gene sequences from 186 specimens were amplified,and 6 subtypes were identified,including CRF07_BC(96,57.6%),CRF01_AE(58,31.2%),CRF08_BC(22,11.8%),CRF85_BC(2,1.1%),CRF55_01B(5,2.7%),and CRF01_AE/CRF07_BC(3 cases of unique recombinant form,1.6%).At the gene threshold of 0.75%,a total of 20 molecular clusters were formed and 55 sequences(55/186,29.6%)were accessed to the network.The largest molecular cluster C1 contained 13 cases,12 cases of that were≥50 years old,and 10 cases(76.9%)carried the NNRTI resistant mutation K103 N.The C2 molecular cluster was a collection of four students,and they were all infected through homosexual behavior transmission.There were drug resistance mutations in 25 cases,with a pre-treatment drug resistance rate of 13.4%(25/186).Among them,four cases were NRTI resistant mutations,including T69D,T215S/TA,and L74I.21 cases were NNRTIs resistant mutations,including K103 N,E138A/EV/G,P225PH,and Y188F.Four cases were PI resistant mutations,including L90LM,M46I,K20KT,and N88 ND.Conclusions CRF07_BC subtype spreads continuously through high-risk groups.Elderly cluster≥50 years old with inferred transmission and MSM infected cluster are the primary intervention targets in Shaoxing City,and more effective interventions are needed to prevent virus spread.