2022—2024年四川省自贡市新报告HIV-1感染者基因亚型及治疗前耐药特征分析

Genetic subtypes and pretreatment drug resistance of newly reported HIV-1 infection cases in Zigong, Sichuan, 2022−2024

  • 摘要:
    目的 了解四川省自贡市新报告HIV-1感染者基因亚型的流行特征及治疗前耐药情况,为制定个体化治疗方案和有效的干预措施提供科学依据。
    方法 收集2022—2024年自贡市新报告HIV-1感染者血浆样本及人口学信息,扩增pol区获取基因序列,构建进化树判定基因亚型,并上传序列至美国斯坦福大学HIV耐药数据库,分析耐药情况。以0.5%基因距离作为阈值构建分子传播网络,分析耐药传播特点及网络关联情况。
    结果  共获得pol区基因序列1 523条,基因亚型主要为CRF07_BC(52.26%)、CRF01_AE(22.72%)、CRF08_BC(16.41%)、CRF85_BC(4.01%);不同基因亚型的HIV-1 感染者在年龄(χ2=39.665,P<0.001)、文化程度(χ2=10.657,P=0.031)、传播途径(χ2=21.403,P=0.006)和耐药状态方面(χ2=52.520,P<0.001)比较差异均有统计学意义。对1 523例HIV样本进行的耐药性监测显示,共有173例样本出现不同程度的耐药,总耐药率为11.35%(173/1 523)。非核苷类逆转录酶抑制剂(NNRTIs)类耐药率为7.81%(119/1 523),核苷类逆转录酶抑制剂(NRTIs)耐药率为1.31%(20/1 523),蛋白酶抑制剂(PIs)耐药率为1.51%(23/1 523)。NNRTIs类耐药突变位点以K103和E138为主, K103N/KN/KNRS、E138A/EA/EG/EK/K在出现的组合突变位点中占比较高;按照0.5%基因距离计算,有705条序列入网(入网率46.29%),共形成150个分子簇,CRF07_BC亚型成簇率最高,存在2个耐药传播簇,Q58E和M46I为主要突变位点。此外,还监测到CRF85_BC亚型中存在的1个大型耐药传播簇有13个节点,E138A为主要突变位点。
    结论  自贡市HIV-1感染者病毒基因亚型流行种类复杂,应关注重点传播分子簇,采取必要的干预措施,阻止HIV-1疫情的传播。同时,HIV-1感染者抗病毒治疗前耐药率达到中等水平,应把治疗前耐药监测纳入监测管理,通过对耐药突变位点的分析,明确不同亚型的耐药特点及其对治疗的影响。

     

    Abstract:
    Objective  To understand the spread characteristics and pre-treatment drug resistance of HIV-1 in newly reported HIV-1 infection cases in Zigong, Sichuan province, and provide scientific evidence for the development of individualized treatment programs and effective interventions.
    Methods Collect plasma samples and demographic information from newly reported HIV-1 infected individuals in Zigong City from 2022 to 2024, amplify the pol region to obtain gene sequences, construct a phylogenetic tree to determine genetic subtypes, and upload the sequences to the Stanford University HIV Drug Resistance Database in the USA to analyze drug resistance. Using a 0.5% genetic distance as the threshold, construct a molecular transmission network to analyze the characteristics of drug resistance transmission and network associations.
    Results A total of 1 523 pol gene region sequences were obtained, the main genetic subtypes were CRF07_BC ( 52.26%), CRF01_AE ( 22.72%), CRF08_BC ( 16.41%), and CRF85_BC ( 4.01%). There were significant differences among different genetic subtypes in terms of age (χ2=39.665, P<0.001), educational level (χ2=10.657, P=0.031), transmission route (χ2=21.403, P=0.006), and drug resistance status (χ2=52.520, P<0.001) of the HIV-1 infection cases. Drug resistance monitoring of 1 523 samples from HIV-1 infection cases showed that 173 samples had varying degrees of drug resistance, with an overall drug resistance rate of 11.35%. The drug resistance rate was 7.81% (119/1 523) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 1.31% (20/1 523) for nucleoside reverse transcriptase inhibitors (NRTIs) and 1.51% (23/1 523) for protease inhibitors (PIs). The main drug resistance mutation loci of NNRTIs were K103 and E138, and the combined mutation loci with relatively high proportions were K103N/KN/KNRS and E138A/EA/EG/EK/K. Based on the genetic distance of 0.5%, 705 sequences were enrolled in the network (46.29%), forming 150 molecular clusters. Subtype CRF07_BC had the highest clustering rate. There were 2 drug-resistant transmission clusters, with Q58E and M46I as the main mutation loci. In addition, a large drug-resistant transmission cluster with 13 nodes was also detected in subtype CRF85_BC, with E138A as the main mutation locus.
    Conclusion The circulating subtypes of HIV-1 in Zigong were complex. It is necessary to pay attention to the key transmission molecular clusters and take necessary interventions to prevent the spread of HIV-1 infection. Meanwhile, the drug resistance rate of HIV-1 infection cases before antiviral treatment reached a medium level. Pretreatment drug resistance monitoring should be included in the management of HIV infection cases. Through the analysis on drug resistance mutation loci, the drug resistance characteristics of different subtypes and their impact on treatment can be clarified.

     

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