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Article(id=1241023940781470543, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241023927812682133, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202410311, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1729180800000, receivedDateStr=2024-10-18, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773812764591, onlineDateStr=2026-03-18, pubDate=1739116800000, pubDateStr=2025-02-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773812764591, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773812764591, creator=13701087609, updateTime=1773812764591, updator=13701087609, issue=Issue{id=1241023927812682133, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='3', pageStart='385', pageEnd='576', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773812761500, creator=13701087609, updateTime=1773812858867, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241024336258200259, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241023927812682133, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241024336258200260, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241023927812682133, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=547, endPage=551, ext={EN=ArticleExt(id=1241023941137986416, articleId=1241023940781470543, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Analysis of the molecular transmission network of the new recombinant HIV type cRF105_0108 in Luzhou from 2017 to 2023, columnId=1228016573156360233, journalTitle=Modern Preventive Medicine, columnName=Disease Control and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the transmission characteristics of the CRF105_0108 subtype in Luzhou, aiming to provide a scientific basis for effective control of its spread in the region.

Methods

Genetic sequences obtained from drug-resistant testing of antiretroviral therapy failures among AIDS/HIV patients in Luzhou from 2017 to 2023 were collected for subtype and genotype resistance analysis. The molecular transmission network of CRF105_0108 was constructed using genetic distance methods, and factors influencing network inclusion were analyzed.

Results

A total of 61 CRF105_0108 gene sequences were obtained. A molecular transmission network was constructed at a 1.5% genetic distance, achieving an inclusion rate of 80.33%(49/61), forming 3 molecular clusters and 247 edges. A high-resolution molecular transmission network was constructed at a 0.6% genetic distance, with an inclusion rate of 40.98% (25/61), forming 9 molecular clusters and 22 edges. Univariate analysis indicated a statistically significant difference in network inclusion based on different residential locations (χ2=12.739, P=0.025), while differences in gender and other factors were not statistically significant. The genotype resistance rate for the CRF105_0108 subtype was 54.10% (33/61), with 8 samples exhibiting dual resistance to NRTI and NNRTI.

Conclusion

The transmission of the CRF105_0108 subtype in Luzhou may have formed a large transmission cluster. It is recommended to conduct genetic subtype monitoring and pre-treatment resistance testing for newly reported AIDS/HIV patients, to dynamically monitor the constructed transmission network, and to implement timely intervention measures for high-risk transmitters, thereby enhancing the specificity of antiretroviral therapy and improving the precision of prevention and control efforts.

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目的

分析CRF105_0108亚型在泸州市的传播特征，以期为有效控制其在该地区的传播提供科学依据。

方法

收集2017—2023年泸州市AIDS/HIV感染者中抗病毒治疗失败人群耐药检测获得的基因序列进行亚型分析和基因型耐药分析，使用基因距离法构建CRF105_0108亚型分子传播网络并分析入网的影响因素。

结果

共获得61条CRF105_0108亚型基因序列。按照1.5%基因距离构建分子传播网络，入网率80.33%（49/61），形成3个分子簇，247个边；按照0.6%基因距离构建高分辨分子传播网络，入网率40.98%（25/61），形成9个分子簇，22条边；单因素分析显示不同居住地的入网差异具有统计学意义（χ2=12.739, P=0.025），性别等其他因素差异无统计学意义。CRF105_0108亚型基因型耐药率为54.10%（33/61），8例样本表现对NRTI和NNRTI双重耐药。

结论

CRF105_0108亚型在泸州的传播可能已经形成一个大的传播簇，建议对新报告AIDS/HIV感染者开展基因亚型监测和治疗前耐药监测，对本次研究构建的分析传播网络进行动态监测，对高风险传播者及时开展干预措施，同时使抗病毒治疗更具针对性，提高防控的精准性。

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曾沛斌，E-mail:
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艾雨（1996—），女，硕士在读，主管技师，研究方向：公共卫生

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艾雨（1996—），女，硕士在读，主管技师，研究方向：公共卫生

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Chinese Journal of Health Laboratory Technology, 2022, 32(24):2990-2993.(In Chinese), articleTitle=Analysis of molecular subtypes and drug resistance of newly confirmed HIV-1 infected persons in Huzhou City in 2021, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1241023943692316676, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, xref=1., ext=[AuthorCompanyExt(id=1241023943704899589, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, companyId=1241023943692316676, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=West China School of Public Health, Sichuan University / West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China), AuthorCompanyExt(id=1241023943709093895, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, companyId=1241023943692316676, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.四川大学华西公共卫生学院/华西第四医院，四川 成都 610041)]), AuthorCompany(id=1241023943822340114, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, xref=2., ext=[AuthorCompanyExt(id=1241023943839117333, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, companyId=1241023943822340114, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.泸州市疾病预防控制中心，四川 泸州 646000)])], figs=[ArticleFig(id=1241023946821267725, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, language=EN, label=Figure 1, caption=CRF105_0108 pol region phylogenetic tree, figureFileSmall=CEwEIIV3Ro08k4JK8aav/g==, figureFileBig=CgbW1fakbBrUqcKjUyl+qg==, tableContent=null), ArticleFig(id=1241023946900959508, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, language=CN, label=图1, caption=CRF105_0108pol区系统进化树, figureFileSmall=CEwEIIV3Ro08k4JK8aav/g==, figureFileBig=CgbW1fakbBrUqcKjUyl+qg==, tableContent=null), ArticleFig(id=1241023947148423464, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, language=EN, label=Figure 2, caption=Molecular network propagation characteristics, figureFileSmall=iKJokAC8oxBjUFRP7qItZA==, figureFileBig=lzFzKymxueiozyotZ9IOUA==, tableContent=null), ArticleFig(id=1241023947291029813, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, language=CN, label=图2, caption=分子网络传播特征图, figureFileSmall=iKJokAC8oxBjUFRP7qItZA==, figureFileBig=lzFzKymxueiozyotZ9IOUA==, tableContent=null), ArticleFig(id=1241023947395887424, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, language=EN, label=Table 1, caption=

Analysis of the molecular transmission network for CRF105_0108 subtype in Luzhou

, figureFileSmall=null, figureFileBig=null, tableContent=
变量人口学特征合计是否入网（d=0.6%)χ2值P值
是否
性别男4016240.0460.829
女21912
年龄（岁）31～406154.0280.409
41～50945
51～601578
61～7017512
>701486
婚姻状况未婚3121.3160.626
已婚或有配偶291019
离异或丧偶291415
文化程度文盲13581.0790.589
小学401822
初中及以上826
感染途径途径异性传播614912——
职业农民5322311.6750.519
家政、家务及待业514
商业服务121
样本来源检测咨询2111.5820.711
其他就诊者检测27918
阳性者配偶或性伴检测633
其他261214
居住地江阳区71612.7390.025
龙马潭区303
纳溪区532
合江县606
泸县261412
叙永县1275
古蔺县202
), ArticleFig(id=1241023947504939337, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, language=CN, label=表1, caption=

泸州市CRF105_0108亚型毒株分子传播网络分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变量人口学特征合计是否入网（d=0.6%)χ2值P值
是否
性别男4016240.0460.829
女21912
年龄（岁）31～406154.0280.409
41～50945
51～601578
61～7017512
>701486
婚姻状况未婚3121.3160.626
已婚或有配偶291019
离异或丧偶291415
文化程度文盲13581.0790.589
小学401822
初中及以上826
感染途径途径异性传播614912——
职业农民5322311.6750.519
家政、家务及待业514
商业服务121
样本来源检测咨询2111.5820.711
其他就诊者检测27918
阳性者配偶或性伴检测633
其他261214
居住地江阳区71612.7390.025
龙马潭区303
纳溪区532
合江县606
泸县261412
叙永县1275
古蔺县202
), ArticleFig(id=1241023947618185557, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, language=EN, label=Table 2, caption=

Distribution of CRF105_0108 subtype genotype resistance mutation sites in Luzhou

, figureFileSmall=null, figureFileBig=null, tableContent=
突变位点类型耐药相关突变位点突变数（%）
PI突变1（0.97）
I47V1（0.97）
NRTI突变18（17.48）
K65R3（2.91）
D67DN1（0.97）
S68G/SN4（3.88）
K70E/KT2（1.94）
Y115F1（0.97）
M184V/MV7（6.80）
NNRTI突变84（81.55）
L100I2（1.94）
V106I/M/VI/VIM8（7.77）
E138A/EG/EK4（3.88）
V179D/DE/VD61（59.22）
Y181C1（0.97）
Y188L/YC5（4.85）
H221HY1（0.97）
P225H1（0.97）
F227L1（0.97）
), ArticleFig(id=1241023947785957724, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241023940781470543, language=CN, label=表2, caption=

泸州市CRF105_0108亚型基因型耐药突变位点分布

, figureFileSmall=null, figureFileBig=null, tableContent=
突变位点类型耐药相关突变位点突变数（%）
PI突变1（0.97）
I47V1（0.97）
NRTI突变18（17.48）
K65R3（2.91）
D67DN1（0.97）
S68G/SN4（3.88）
K70E/KT2（1.94）
Y115F1（0.97）
M184V/MV7（6.80）
NNRTI突变84（81.55）
L100I2（1.94）
V106I/M/VI/VIM8（7.77）
E138A/EG/EK4（3.88）
V179D/DE/VD61（59.22）
Y181C1（0.97）
Y188L/YC5（4.85）
H221HY1（0.97）
P225H1（0.97）
F227L1（0.97）
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2017—2023年泸州地区HIV新重组型CRF105_0108分子传播网络分析
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艾雨 1, 2 , 余明 2 , 许文平 2 , 曾沛斌 1
现代预防医学 | 疾病预防控制 2025,52(3): 547-551
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现代预防医学 | 疾病预防控制 2025, 52(3): 547-551
2017—2023年泸州地区HIV新重组型CRF105_0108分子传播网络分析
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艾雨1, 2, 余明2, 许文平2, 曾沛斌1
作者信息
  • 1.四川大学华西公共卫生学院/华西第四医院，四川 成都 610041
  • 2.泸州市疾病预防控制中心，四川 泸州 646000

    • 艾雨（1996—），女，硕士在读，主管技师，研究方向：公共卫生

通讯作者:

曾沛斌，E-mail:
Analysis of the molecular transmission network of the new recombinant HIV type cRF105_0108 in Luzhou from 2017 to 2023
Yu AI1, 2, Ming YU2, Wen-ping XU2, Pei-bin ZENG1
Affiliations
  • West China School of Public Health, Sichuan University / West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China
出版时间: 2025-02-10 doi: 10.20043/j.cnki.MPM.202410311
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摘要
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目的

分析CRF105_0108亚型在泸州市的传播特征，以期为有效控制其在该地区的传播提供科学依据。

方法

收集2017—2023年泸州市AIDS/HIV感染者中抗病毒治疗失败人群耐药检测获得的基因序列进行亚型分析和基因型耐药分析，使用基因距离法构建CRF105_0108亚型分子传播网络并分析入网的影响因素。

结果

共获得61条CRF105_0108亚型基因序列。按照1.5%基因距离构建分子传播网络，入网率80.33%（49/61），形成3个分子簇，247个边；按照0.6%基因距离构建高分辨分子传播网络，入网率40.98%（25/61），形成9个分子簇，22条边；单因素分析显示不同居住地的入网差异具有统计学意义（χ2=12.739, P=0.025），性别等其他因素差异无统计学意义。CRF105_0108亚型基因型耐药率为54.10%（33/61），8例样本表现对NRTI和NNRTI双重耐药。

结论

CRF105_0108亚型在泸州的传播可能已经形成一个大的传播簇，建议对新报告AIDS/HIV感染者开展基因亚型监测和治疗前耐药监测，对本次研究构建的分析传播网络进行动态监测，对高风险传播者及时开展干预措施，同时使抗病毒治疗更具针对性，提高防控的精准性。

HIV-1  /  CRF105_0108亚型  /  分子传播网络  /  基因型耐药
Objective

To analyze the transmission characteristics of the CRF105_0108 subtype in Luzhou, aiming to provide a scientific basis for effective control of its spread in the region.

Methods

Genetic sequences obtained from drug-resistant testing of antiretroviral therapy failures among AIDS/HIV patients in Luzhou from 2017 to 2023 were collected for subtype and genotype resistance analysis. The molecular transmission network of CRF105_0108 was constructed using genetic distance methods, and factors influencing network inclusion were analyzed.

Results

A total of 61 CRF105_0108 gene sequences were obtained. A molecular transmission network was constructed at a 1.5% genetic distance, achieving an inclusion rate of 80.33%(49/61), forming 3 molecular clusters and 247 edges. A high-resolution molecular transmission network was constructed at a 0.6% genetic distance, with an inclusion rate of 40.98% (25/61), forming 9 molecular clusters and 22 edges. Univariate analysis indicated a statistically significant difference in network inclusion based on different residential locations (χ2=12.739, P=0.025), while differences in gender and other factors were not statistically significant. The genotype resistance rate for the CRF105_0108 subtype was 54.10% (33/61), with 8 samples exhibiting dual resistance to NRTI and NNRTI.

Conclusion

The transmission of the CRF105_0108 subtype in Luzhou may have formed a large transmission cluster. It is recommended to conduct genetic subtype monitoring and pre-treatment resistance testing for newly reported AIDS/HIV patients, to dynamically monitor the constructed transmission network, and to implement timely intervention measures for high-risk transmitters, thereby enhancing the specificity of antiretroviral therapy and improving the precision of prevention and control efforts.

HIV-1  /  CRF105_0108 subtype  /  Molecular transmission network  /  Genotype resistance
艾雨, 余明, 许文平, 曾沛斌. 2017—2023年泸州地区HIV新重组型CRF105_0108分子传播网络分析. 现代预防医学, 2025 , 52 (3) : 547 -551 . DOI: 10.20043/j.cnki.MPM.202410311
Yu AI, Ming YU, Wen-ping XU, Pei-bin ZENG. Analysis of the molecular transmission network of the new recombinant HIV type cRF105_0108 in Luzhou from 2017 to 2023[J]. Modern Preventive Medicine, 2025 , 52 (3) : 547 -551 . DOI: 10.20043/j.cnki.MPM.202410311
正文
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人类免疫缺陷病毒（human immunodeficiency virus, HIV）感染人体后，会导致以T淋巴细胞免疫功能缺失为主的获得性免疫缺陷综合症（acquired immune deficiency syndrome, AIDS），又称艾滋病。HIV主要分为两种类型HIV-1和HIV-2。HIV-1具有极高的变异性，可细分为多个亚型，并且不同亚型之间会发生病毒重组，根据Los Alamos国家实验室的HIV基因数据库显示目前全球已有157种已鉴定的循环重组型（circular reorganization forms, CRFs）[1]和大量独特重组型（unique reorganization forms, URFs）。在全球范围内，C亚型的感染人数最多，其次是CRFs、B亚型、A亚型、URFs及其他亚型，其中重组病毒的感染率高达22.8%，且该比例仍在上升[2]。
在四川省的HIV分子流行病学监测中，CRF07_BC亚型占据了全省HIV流行的主导地位，超过50%，其次为CRF01_AE和CRF08_BC，后者的比例不超过10%[3-4]。泸州市位于川渝和云贵四省的交界，HIV传播风险较为复杂。与全省HIV亚型的总体分布相比，泸州地区的HIV亚型分布展现出独特的特征。调查结果表明，泸州地区的CRF08_BC亚型与CRF07_BC、CRF01_AE这两种亚型的比例相近，已成为该地区的主要流行株[5]。
CRF105_0108亚型是2019年在凉山州首次被监测到的新重组株，早期调查显示其在泸州市存在快速传播的风险[5-6]。本研究收集了2017—2023年泸州市HIV/AIDS感染者中抗病毒治疗失败人群的耐药检测结果，获得了CRF105_0108亚型的基因序列，并通过分子传播网络分析技术探讨了该亚型毒株在泸州市的传播特征，以期为有效控制其在该地区的传播提供科学依据。
1　对象与方法
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1.1　对象
1.1.1　样本来源
收集2017—2023年泸州市AIDS/HIV感染者中抗病毒治疗失败（接受艾滋病抗病毒治疗6个月及以上、HIV-1病毒载量结果>1 000拷贝数/ml）人群耐药检测获得的判定为CRF105_0108基因序列共61条纳入研究。本研究获得泸州市疾病预防控制中心伦理委员会批准。
1.1.2　信息来源
样本信息转自中国疾病预防控制中心艾滋病综合防治信息系统。主要包括性别、年龄、婚姻状况、职业、现住址、感染途径、样本来源等。
1.2　方法
1.2.1　核酸提取和基因扩增
测序参照中国疾病预防控制中心《HIV-1基因型耐药检测及质量保证指南（2013年版）》操作说明和试剂盒说明书。
1.2.2　基因亚型分析
测序获得的pol区基因序列，通过HIV-BLAST在线工具（https://www.hiv.lanl.gov/content/sequence/BASIC_BLAST/basic_blast.html）对HIV-1进行初步分型鉴定。Fasttree软件构建ML系统进化树，进行亚型校正；Figtree软件进化树的展示。
1.2.3　构建传播网络
使用HyPhy2.2.4软件和Tamura-Nei 93（TN93）模型计算两条序列间的基因距离（pairwise genetic distance, d），构建基因距离阈值从0.1%～ 2.0%范围内所有网络，由于本研究中样本时间跨度较大，以d=1.5%作为阈值分析传播网络中所有感染者间的传播关联；同时选择产生分子网络数量最多的基因距离（d=0.6%）作为最敏感阈值，用于构建高分辨率分子网络[7]。使用Cytoscape v3.9.1计算分子网络相关参数及传播网络，找到潜在的传播点。其中:度是分子传播网络中某节点与其他节点通过边连接的数目；两个及以上的节点相连形成簇，成簇是指与至少一个节点相连构建传播网络；入网率是进入分子传播网络的人数占总人数的百分比。
1.2.4　基因型耐药分析
将序列提交到美国斯坦福大学HIV耐药数据库（HIVdb Program: Sequence Analysis - Stanford Coronavirus Antiviral & Resistance Database (CoVDB)）进行耐药程度分析，根据数据库系统评分将耐药程度分为敏感(S)、潜在低度耐药(P)、低度耐药(L)、中度耐药(I)和高度耐药(H)5个水平，其中后3个水平判定毒株为耐药毒株。耐药率=对抗病毒药物发生低度及以上耐药的样本数/研究总样本数×100%。
1.3　统计分析
使用SPSS 26.0进行统计分析。分析研究对象HIV-1分子传播网络的入网率的影响因素，单因素采用χ2检验或Fisher精确检验，多因素采用二分类logistic回归，双侧检验，检验水准α=0.05。
2　结果
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2.1　基本特征
共收集到CRF105_0108亚型序列61条，其中以男性（40/61，65.57%）、农民（53/61，86.89%）、50岁以上年龄（46，75.41%）、小学及以下文化程度（53/61，86.89%）、居住地为泸县（26/61，42.62%）为主，所有病例均报告为异性传播。见表1。
2.2　基因进化树分析
将收集到的CRF105_0108亚型与本地其他常见亚型CRF07_BC、CRF01_AE、CRF08_BC、CRF55_01B、CRF85_BC构建系统进化树，可见CRF105_0108亚型单独成簇。见图1。
2.3　分子传播网络及影响因素分析
按照1.5%基因距离构建分子传播网络，共49个病例进入网络，入网率80.33%（49/61），形成3个分子簇，247个边。本研究中3个传播簇的节点均大于2，节点中位数为8，节点度值中位数为8，P25～P75（3～15）。按照0.6%基因距离构建高分辨分子传播网络，共25个病例进入网络，入网率40.98%（25/61），形成9个分子簇，22条边。44.44%（4/9）的分子簇节点数大于2，其中最大节点数为6。节点度值最大为5，半数以上节点（52.00%，13/25）仅通过一条边与另一节点相连构成网络；有2条以上边的4个节点中以男性（3/4，75.00%）、50岁以上年龄（3/4，75.00%）、小学及以下文化程度（4/4，100.00%）、农民（4/4，100.00%）、已婚或有配偶（3/4，75.00%）、来源叙永县（3/4，75.00%）为主。见图2。将不同性别、年龄、婚姻状况、文化程度、职业、样本来源、居住地入网率进行单因素χ2分析显示，不同居住地的入网差异具有统计学意义（χ2=12.739, P=0.025），性别等其他因素差异无统计学意义，见表1。由于单因素分析中除居住地外的其他因素P值均大于0.2，故未进行进一步的多因素分析。
2.4　基因型耐药分析
本研究61例CRF105_0108亚型样本的基因型耐药率为54.10%（33/61），共检出103个耐药相关位点，其中蛋白酶抑制剂（protease inhibitors, PI）、核苷类逆转录酶抑制剂（nucleoside reverse transcriptase inhibitors, NRTI）、非核苷类逆转录酶抑制剂（non-nucleoside reverse transcriptase inhibitors, NNRTI）的耐药率分别为1.64%（1/61），13.11%（8/61）和52.46%（32/61）。8例样本表现对NRTI和NNRTI双重耐药。具体突变位点见表2。
3　讨论
收起
CRF105_0108亚型是近年发现的新HIV-1毒株，是第一个由CRF08_BC和CRF01_AE重组产生的CRF，系统进化分析显示其是一个CRF08_BC的片段插入CRF01_AE骨架，在pol区有一个重组断点[6]。
本研究收集2017—2023年泸州市AIDS/HIV感染者抗病毒治疗失败人群耐药检测获得的判定为CRF105_0108亚型基因序列，发现泸州市CRF105_0108亚型HIV-1毒株以男性、农民、50岁以上、小学及以下文化程度、异性传播为主，与当地总体疫情相一致[8]。42.62%的CRF105_0108亚型病例来自于泸县，提示该毒株在该辖区内的流行形势较为严峻，应该在当地采取针对性措施进行干预，控制其进一步扩散。
随着分子流行病学的发展，基于HIV基因序列遗传学相似性构建的分子网络在艾滋病防控领域得到广泛应用，可揭示HIV感染者的传播关系和传播模型、识别近期出现的快速传播簇、预测高风险网络，为艾滋病精准干预和防控提供了有效的技术手段[8]。本研究使用两种不同的基因距离构建分子网络，以d=1.5%作为阈值尽可能分析传播网络中所有感染者间的传播关联，同时以d=0.6%作为阈值高分辨率分析传播网络感染者间的潜在传播关联。当使用1.5%基因距离构建分子传播网络探究所有感染者的传播关联时发现，泸州市CRF105_0108亚型的入网率达到80.33%，与此前的一项研究相似[5]。说明从长远来看，造成泸州市CRF105_0108亚型毒株的流行的原因有可能是由某一个或多个关键传播者所引起的。建议当地可以将分子传播网络分析与传统流行病学相结合，进一步追踪关键传播者，有效控制CRF105_0108亚型毒株的进一步传播。
根据流行病学调查信息，本研究中所有病例均为异性传播，但是在高分辨的分子传播网络（0.6%基因距离）中，发现了仅有男性构成的分子网络。一方面可能是存在还未被发现的链接两个男性的女性病例，另一方面由于性行为信息是感染者提供，由于隐私及歧视可能存在报告偏倚，所以也需要警惕CRF105_0108亚型毒株是否已经在MSM人群中开始传播。
本研究对高分辨分子传播网络（d=0.6%）入网影响因素的分析发现，不同居住地的CRF105_0108亚型病例入网率差异具有统计学意义。虽然每个区县均有CRF105_0108亚型毒株，但是入网病例主要集中在泸县（14/25）和叙永县（7/25），纳溪区（3/25）和江阳区（1/25）也有病例入网，其余区县无病例入网。
本研究中CRF105_0108基因型耐药率为54.10%。高于既往本地区研究中50岁以上抗病毒失败人群的耐药率51.09%[9]。V179D/E是多态性辅助NNRTI选择的突变，其单独出现时，不会导致低度及以上耐药，但与其他NNRTI耐药相关突变共同出现时，会使依非韦伦（EFV）、依曲韦林（ETR）、奈韦拉平（NVP）、利匹韦林（RPV）的敏感性降低[10]。K103R/KR是一种多态性突变，其单独对NNRTI易感性没有影响，在斯坦福耐药数据库分类中归属于RT其他突变，不属于耐药监测突变[11]，故在大多对基因型耐药的研究中，并未对其关注。然而，当K103R/KR与V179D联合使用时可以使NVP和EFV敏感性降低。以往有研究发现，一些新出现的流行重组毒株本身就携带耐药相关突变。CRF55_01B毒株天然含有V179E突变，与多态性突变E138G组合，造成5%～15%的CRF55_01B毒株对EFV/NVP低度耐药[12-13]。CRF65_cpx毒株天然有V179D（96.9%）突变，与K103R多态性突变组合，导致对EFV/NVP中度耐药（21.9%）[14]。本研究中所有CRF105_0108序列均存在V179位点突变，建议进一步对该亚型的HIV耐药突变位点进行研究，探索该位点是否与CRF105_0108亚型是否具有相关性。此外，本研究中仅V179位点出现突变，无其他NNRTI突变的44例样本中中有15例判定为NNRTI耐药株，在对序列进一步研究发现，该15例毒株中K103R/KR与V179D同时出现，导致对NVP和EFV出现中度耐药，对RPV出现低度耐药。在湖州市的一项研究中也发现过1例感染者同时出现K103R与V179D耐药突变而导致的耐药[15]。这提示在对HIV毒株进行基因型耐药研究时，除了常规耐药检测的基因位点外，还需要密切关注其他可能会与耐药相关突变位点发生协同作用的其他突变。
综上所述，本研究通过对2017—2023年泸州市CRF105_0108亚型AIDS/HIV感染者基本情况进行分析，发现其均携带V179位点突变且在泸州的传播可能已经形成一个大的传播簇，建议对该地区新报告AIDS/HIV感染者开展基因亚型和治疗前耐药监测。一方面对本次研究构建的分析传播网络进行动态监测，一旦发现网络扩张，对高风险传播者及时开展干预措施；另一方面使抗病毒治疗更具针对性，提高防控的精准性有效性。
本研究样本序列来源于泸州市AIDS/HIV感染者抗病毒失败人群耐药检测，所获得的序列样本量有限。对于长期规范服药、治疗效果良好的感染人群，我们无法获得其感染毒株序列，所以本研究结果可能存在一定局限性。
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doi: 10.20043/j.cnki.MPM.202410311
  • 接收时间：2024-10-18
  • 首发时间：2026-03-18
  • 出版时间：2025-02-10
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    1.四川大学华西公共卫生学院/华西第四医院，四川 成都 610041
    2.泸州市疾病预防控制中心，四川 泸州 646000

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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