Article(id=1240977216234910477, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240977214964036360, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202412496, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1735228800000, receivedDateStr=2024-12-27, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773801624592, onlineDateStr=2026-03-18, pubDate=1748102400000, pubDateStr=2025-05-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773801624592, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773801624592, creator=13701087609, updateTime=1773801624592, updator=13701087609, issue=Issue{id=1240977214964036360, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='10', pageStart='1729', pageEnd='1920', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773801624289, creator=13701087609, updateTime=1773825591019, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241077738770068227, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240977214964036360, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241077738770068228, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240977214964036360, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1902, endPage=1908, ext={EN=ArticleExt(id=1240977216541094671, articleId=1240977216234910477, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Molecular transmission network characteristics and drug resistance analysis of 123 newly reported HIV-1 cases, Guiyang City, columnId=1228016573156360233, journalTitle=Modern Preventive Medicine, columnName=Disease Control and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the molecular transmission network characteristics and drug resistance of newly reported human immunodeficiency virus type 1 (HIV-1) infected individuals in Guiyang City, to provide a basis for epidemic trends and preventive and control measures.

Methods

Blood samples and demographic information of newly reported HIV-1 infected individuals who did not receive antiviral therapy in Guiyang City from 2021 to 2023 were collected. The obtained pol region gene sequences were uploaded to the Stanford University HIV drug resistance database for genotype and drug resistance analysis, and molecular transmission network was constructed based on the optimal gene distance (d=1.5%) and analyzed for factors influencing entry into the network.

Results

A total of 171 samples were collected, and 123 (71.93%) were successfully amplified to obtain valid sequences. Six genotypes were found, mainly CRF07_BC (54.5%, 67/123) and CRF01_AE (24.4%, 30/123). A total of 38 sequences were integrated into the network, with an integration rate of 30.89%. 13 molecular clusters were formed, and the number of cases in the clusters ranged from 2 to 9. Multivariate Logistic regression results showed that heterosexual transmission, CRF07_BC and CRF01_AE were more likely to enter the network(P<0.05). CRF07_BC in Chongqing, Guangxi, Yunnan and Guiyang had cross-regional transmission. The drug resistance rate of 123 samples before treatment was 17.07% (21/123), the drug resistance rates were 7.32% for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 3.25% for nucleoside reverse transcriptase inhibitors (NRTIs), 3.25% for protease inhibitors (PIs), and four samples showed dual drug resistance.

Conclusion

The genotypes of newly reported HIV-1 infected individuals in Guiyang were mainly CRF07_BC and CRF01_AE. CRF07_BC is closely related to Chongqing and Guangxi. The drug resistance rate of HIV-1 before treatment was high. In the future, we should continue to build molecular transmission networks for long-term monitoring of the area, cooperate with neighboring provinces and cities to take effective AIDS prevention and control measures to further curb the transmission and spread of the virus.

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目的

分析贵阳市新报告人类免疫缺陷病毒-1型(Human Immunodeficiency VirusType 1, HIV-1)感染者分子传播网络特征及耐药情况,为疫情流行趋势和防治措施提供依据。

方法

收集2021—2023年贵阳市新报告未接受抗病毒治疗的HIV-1感染者的血液样本及人口学信息。将获得的pol区基因序列上传到斯坦福大学HIV耐药数据库中进行基因型和耐药分析,基于最适基因距离(d=1.5%)构建分子传播网络并分析入网影响因素。

结果

共收集到171例样本,成功扩增获得有效序列123例(71.93%),发现6种基因型,以CRF07_BC(54.5%,67/123)和CRF01_AE(24.4%,30/123)为主,共有38条序列入网,入网率为30.89%,形成13个分子簇,簇内病例数在2~9例之间。多因素logistic回归结果显示,异性传播、CRF07_BC和CRF01_AE的感染者更容易入网(P<0.05)。重庆、广西、云南的CRF07_BC与贵阳市存在跨地区传播。123例样本的治疗前耐药率为17.07%(21/123),非核苷类逆转录酶抑制剂(NNRTIs)耐药率7.32%,核苷类逆转录酶抑制剂(NRTIs)耐药率3.25%,蛋白酶抑制剂(PI)耐药率3.25%,4例样本存在双重耐药。

结论

贵阳市新报告HIV-1感染者基因型以CRF07_BC和CRF01_AE为主,CRF07_BC与重庆、广西存在着紧密联系,HIV-1治疗前耐药率较高。今后应继续构建分子传播网络对该地区进行长期监测,与周边省市合作采取有效的艾滋病防控措施,进一步遏制病毒传播和蔓延。

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马璐,E-mail:
, copyrightStatement=本刊刊出的所有文章不代表中华预防医学会和本刊编委会的观点,除非特别声明。, copyrightOwner=中华预防医学会和四川大学华西公共卫生学院, extLink=null, articleAbsUrl=null, sourceXml=th2LaSUq4TQ3TVNypl5zqw==, magXml=H4YEL38NG7ORCCctPLXMZw==, pdfUrl=null, pdf=R0KYC1Go6gUQ6/bp7W9QQw==, pdfFileSize=1017641, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=2xPt/6jbIClzCVJw48zPOw==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=5U+ximy4L9/83pH7qFQS6A==, mapNumber=null, authorCompany=null, fund=null, authors=

申万敏(1998—),女,硕士在读,研究方向:疾病预防与控制

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申万敏(1998—),女,硕士在读,研究方向:疾病预防与控制

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(In Chinese), articleTitle=HIV-1 drug resistance and subtype epidemic characteristics of 266 newly confirmed HIV/AIDS patients before antiviral treatment in Guiyang, refAbstract=null)], funds=[Fund(id=1240996920848601940, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, awardId=gzwkj2021-435, language=CN, fundingSource=贵州省卫生健康委科学技术基金项目[贵州省2021年度科学技术基金项目(2021)](gzwkj2021-435), fundOrder=null, country=null), Fund(id=1240996920974431067, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, awardId=gzwkj2021-435, language=CN, fundingSource=应用分子传播网络探讨贵阳市新发HIV/AIDS病例HIV1基因分型及传播特征(gzwkj2021-435), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1240996910958432517, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, xref=1., ext=[AuthorCompanyExt(id=1240996910966821125, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, companyId=1240996910958432517, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Public Health, Guizhou Medical University, Guiyang, Guizhou 550025, China), AuthorCompanyExt(id=1240996910975209734, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, companyId=1240996910958432517, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.贵州医科大学公共卫生与健康学院,贵州 贵阳 550025)]), AuthorCompany(id=1240996911092650260, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, xref=2., ext=[AuthorCompanyExt(id=1240996911105233175, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, companyId=1240996911092650260, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.贵阳市疾病预防控制中心)])], figs=[ArticleFig(id=1240996917937754867, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=EN, label=Fig.1, caption=Molecular network characterization of 123 newly reported HIV-1 infections in Guiyang City, figureFileSmall=KUE7dbaFeZ9hz6t2nuOSeg==, figureFileBig=hzjHgdHQ6Ej243YKWoggNg==, tableContent=null), ArticleFig(id=1240996918004863739, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=CN, label=图1, caption=贵阳市123例新报告HIV-1感染者分子网络特征图

注:C1、C2和C3是分子传播网络中的分子簇,C1为分子网络中节点数最多的,C2是节点数第二多的分子簇,C3是节点数第三多的分子簇。

, figureFileSmall=KUE7dbaFeZ9hz6t2nuOSeg==, figureFileBig=hzjHgdHQ6Ej243YKWoggNg==, tableContent=null), ArticleFig(id=1240996919523201794, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=EN, label=Fig.2, caption=Phylogenetic tree of Guiyang and Chongqing, Yunnan, Sichuan and Guangxi HIV-1 pol regions, figureFileSmall=MFDhtESeaptwX+P4ifd3vA==, figureFileBig=M/szehB9xA/rr+N+/9ngMw==, tableContent=null), ArticleFig(id=1240996919732917002, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=CN, label=图2, caption=贵阳与重庆、云南、四川和广西HIV-1 pol区系统进化树, figureFileSmall=MFDhtESeaptwX+P4ifd3vA==, figureFileBig=M/szehB9xA/rr+N+/9ngMw==, tableContent=null), ArticleFig(id=1240996919846163217, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=EN, label=Fig.3, caption=HIV-1 molecular transmission network between Guiyang and Chongqing, Yunnan, Sichuan and Guangxi, figureFileSmall=WT0M4TwUl1VhstPMwwOREQ==, figureFileBig=ZEXqqMsdUZzJvnNwAoyfFQ==, tableContent=null), ArticleFig(id=1240996919959409433, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=CN, label=图3, caption=贵阳与重庆、云南、四川和广西的HIV-1分子传播网络, figureFileSmall=WT0M4TwUl1VhstPMwwOREQ==, figureFileBig=ZEXqqMsdUZzJvnNwAoyfFQ==, tableContent=null), ArticleFig(id=1240996920072655649, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=EN, label=Table 1, caption=

Analysis of molecular networks and influencing factors of newly reported HIV-1 infections in Guiyang City from 2021 to 2023

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总人数
(构成比/%)
入网数
(占比/%)
单因素分析多因素分析
χ2PaOR(95%CI)P
性别5.7430.017
115(93.5)32(27.8)1.000
8(6.5)6(75.0)4.052(0.19~86.11)0.370
年龄(岁)21.234<0.001
≤2550(40.7)13(26.0)1.000
26~4948(39.0)8(16.7)0.344(0.10~1.17)0.087
≥5025(20.3)17(68.0)4.598(0.18~119.57)0.359
户籍地8.2260.016
本市68(55.3)28(41.2)1.000
本省其他市40(32.5)6(15.0)0.365(0.11~1.25)0.109
外省15(12.2)4(26.7)1.799(0.38~8.48)0.458
婚姻状况8.2800.016
未婚88(71.5)21(23.9)1.000
已婚有配偶24(19.5)13(54.2)0.126(0.01~2.61)0.181
离异或丧偶11(9.0)4(36.4)0.034(0.00~2.59)0.126
民族0.3060.580
汉族100(81.3)32(32.0)
少数民族23(18.7)6(26.1)
文化程度10.1290.001
高中及以下61(49.6)27(44.3)1.000
大专及以上62(50.4)11(17.7)0.723(0.23~2.26)0.577
感染途径24.437<0.001
同性传播91(74.0)17(18.7)1.000
异性传播32(26.0)21(65.6)19.978(1.98~201.44)0.011
毒株亚型22.012<0.001
URF16(13.0)4(25.0)1.000
CRF07_BC67(54.5)11(16.4)10.991(1.06~114.54)0.045
CRF01_AE30(24.4)19(63.3)23.177(2.94~182.58)0.003
其他亚型10(8.1)4(40.0)30.976(2.19~437.62)0.011
), ArticleFig(id=1240996920206873384, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=CN, label=表1, caption=

2021—2023年贵阳市新报告HIV-1感染者入网影响因素分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总人数
(构成比/%)
入网数
(占比/%)
单因素分析多因素分析
χ2PaOR(95%CI)P
性别5.7430.017
115(93.5)32(27.8)1.000
8(6.5)6(75.0)4.052(0.19~86.11)0.370
年龄(岁)21.234<0.001
≤2550(40.7)13(26.0)1.000
26~4948(39.0)8(16.7)0.344(0.10~1.17)0.087
≥5025(20.3)17(68.0)4.598(0.18~119.57)0.359
户籍地8.2260.016
本市68(55.3)28(41.2)1.000
本省其他市40(32.5)6(15.0)0.365(0.11~1.25)0.109
外省15(12.2)4(26.7)1.799(0.38~8.48)0.458
婚姻状况8.2800.016
未婚88(71.5)21(23.9)1.000
已婚有配偶24(19.5)13(54.2)0.126(0.01~2.61)0.181
离异或丧偶11(9.0)4(36.4)0.034(0.00~2.59)0.126
民族0.3060.580
汉族100(81.3)32(32.0)
少数民族23(18.7)6(26.1)
文化程度10.1290.001
高中及以下61(49.6)27(44.3)1.000
大专及以上62(50.4)11(17.7)0.723(0.23~2.26)0.577
感染途径24.437<0.001
同性传播91(74.0)17(18.7)1.000
异性传播32(26.0)21(65.6)19.978(1.98~201.44)0.011
毒株亚型22.012<0.001
URF16(13.0)4(25.0)1.000
CRF07_BC67(54.5)11(16.4)10.991(1.06~114.54)0.045
CRF01_AE30(24.4)19(63.3)23.177(2.94~182.58)0.003
其他亚型10(8.1)4(40.0)30.976(2.19~437.62)0.011
), ArticleFig(id=1240996920315925295, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=EN, label=Table 2, caption=

Distribution of molecular cluster characteristics in more than 2 cases in Guiyang [cases (%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
变量簇1
(n=9)
簇2
(n=6)
簇3
(n=3)
性别
8(88.9)3(50.0)3(100.0)
1(11.1)3(50.0)0(0.0)
年龄(岁)
≤251(11.1)0(0.0)1(33.3)
26~491(11.1)1(16.7)2(66.7)
≥507(77.8)5(83.3)0(0.0)
婚姻状况
未婚2(22.2)1(16.7)3(100.0)
已婚有配偶6(66.7)4(66.6)0(0.0)
离异或丧偶1(11.1)1(16.7)0(0.0)
文化程度
初中及以下8(88.9)5(83.3)0(0.0)
高中或中专0(0.0)1(16.7)0(0.0)
大专及以上1(11.1)0(0.0)3(100.0)
感染途径
同性传播1(11.1)1(16.7)3(100.0)
异性传播8(88.9)5(83.3)0(0.0)
毒株亚型
CRF07_BC0(0.0)0(0.0)3(100.0)
CRF01_AE9(100.0)6(100.0)0(0.0)
接触史
非婚非商业异性性行为2(22.2)2(50.0)0(0.0)
非婚商业异性性行为4(44.5)2(16.6)0(0.0)
男男性行为1(11.1)1(16.7)3(100.0)
配偶或固定性伴阳性2(22.2)1(16.7)0(0.0)
现住址
清镇市9(100.0)6(100.0)0(0.0)
南明区0(0.0)0(0.0)1(33.3)
乌当区0(0.0)0(0.0)2(66.7)
), ArticleFig(id=1240996920429171510, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=CN, label=表2, caption=

贵阳市2例以上病例的分子簇特征分布[例(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
变量簇1
(n=9)
簇2
(n=6)
簇3
(n=3)
性别
8(88.9)3(50.0)3(100.0)
1(11.1)3(50.0)0(0.0)
年龄(岁)
≤251(11.1)0(0.0)1(33.3)
26~491(11.1)1(16.7)2(66.7)
≥507(77.8)5(83.3)0(0.0)
婚姻状况
未婚2(22.2)1(16.7)3(100.0)
已婚有配偶6(66.7)4(66.6)0(0.0)
离异或丧偶1(11.1)1(16.7)0(0.0)
文化程度
初中及以下8(88.9)5(83.3)0(0.0)
高中或中专0(0.0)1(16.7)0(0.0)
大专及以上1(11.1)0(0.0)3(100.0)
感染途径
同性传播1(11.1)1(16.7)3(100.0)
异性传播8(88.9)5(83.3)0(0.0)
毒株亚型
CRF07_BC0(0.0)0(0.0)3(100.0)
CRF01_AE9(100.0)6(100.0)0(0.0)
接触史
非婚非商业异性性行为2(22.2)2(50.0)0(0.0)
非婚商业异性性行为4(44.5)2(16.6)0(0.0)
男男性行为1(11.1)1(16.7)3(100.0)
配偶或固定性伴阳性2(22.2)1(16.7)0(0.0)
现住址
清镇市9(100.0)6(100.0)0(0.0)
南明区0(0.0)0(0.0)1(33.3)
乌当区0(0.0)0(0.0)2(66.7)
), ArticleFig(id=1240996920550806333, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=EN, label=Table 3, caption=

Drug-resistant mutations in HIV-1 infections in Guiyang City

, figureFileSmall=null, figureFileBig=null, tableContent=
样本编号突变位点
NRTIsNNRTIsPI
1226_001T74P
029_S15_L001Q58QE
SentosaBC-12_050L10FI
SentosaBC-6_052V108I
SentosaBC-10_056E138G,V179EI54T
SentosaBC-15_061M184I
SentosaBC-18_064K65R
SentosaBC-22_068M184IE138K
SentosaBC-9_073K238T
SentosaBC-15_078K103N
SentosaBC-16_079M184V
SentosaBC-19_082E138G
SentosaBC-23_086M230I
SentosaBC-12_095M184IF227L
SentosaBC-13_096E138G,V179EM46L
SentosaBC-16_098K103N
SentosaBC-21_101M46L,G73S
SentosaBC-24_103K103N
SentosaBC-4_104D67N
SentosaBC-10_110E138K
SentosaBC-22_121E138K,V179T
), ArticleFig(id=1240996920647275332, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240977216234910477, language=CN, label=表3, caption=

贵阳市HIV-1感染者耐药突变情况

, figureFileSmall=null, figureFileBig=null, tableContent=
样本编号突变位点
NRTIsNNRTIsPI
1226_001T74P
029_S15_L001Q58QE
SentosaBC-12_050L10FI
SentosaBC-6_052V108I
SentosaBC-10_056E138G,V179EI54T
SentosaBC-15_061M184I
SentosaBC-18_064K65R
SentosaBC-22_068M184IE138K
SentosaBC-9_073K238T
SentosaBC-15_078K103N
SentosaBC-16_079M184V
SentosaBC-19_082E138G
SentosaBC-23_086M230I
SentosaBC-12_095M184IF227L
SentosaBC-13_096E138G,V179EM46L
SentosaBC-16_098K103N
SentosaBC-21_101M46L,G73S
SentosaBC-24_103K103N
SentosaBC-4_104D67N
SentosaBC-10_110E138K
SentosaBC-22_121E138K,V179T
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贵阳市123例新报告HIV-1感染者分子传播网络特征及耐药分析
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申万敏 1 , 王大朋 1 , 蒋家俊 2 , 简洁 2 , 林瑞 2 , 刘杨晶 2 , 张羽 2 , 佘敏 2 , 张欐 2 , 袁乡石 2 , 龙世安 1 , 马璐 2
现代预防医学 | 疾病预防控制 2025,52(10): 1902-1908
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现代预防医学 | 疾病预防控制 2025, 52(10): 1902-1908
贵阳市123例新报告HIV-1感染者分子传播网络特征及耐药分析
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申万敏1, 王大朋1, 蒋家俊2, 简洁2, 林瑞2, 刘杨晶2, 张羽2, 佘敏2, 张欐2, 袁乡石2, 龙世安1, 马璐2
作者信息
  • 1.贵州医科大学公共卫生与健康学院,贵州 贵阳 550025
  • 2.贵阳市疾病预防控制中心
  • 申万敏(1998—),女,硕士在读,研究方向:疾病预防与控制

通讯作者:

马璐,E-mail:
Molecular transmission network characteristics and drug resistance analysis of 123 newly reported HIV-1 cases, Guiyang City
Wan-min SHEN1, Da-peng WANG1, Jia-jun JIANG2, jie JIAN2, Rui LIN2, Yang-jing LIU2, Yu ZHANG2, Min SHE2, Li ZHANG2, Xiang-shi YUAN2, Shi-an LONG1, Lu MA2
Affiliations
  • School of Public Health, Guizhou Medical University, Guiyang, Guizhou 550025, China
出版时间: 2025-05-25 doi: 10.20043/j.cnki.MPM.202412496
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目的

分析贵阳市新报告人类免疫缺陷病毒-1型(Human Immunodeficiency VirusType 1, HIV-1)感染者分子传播网络特征及耐药情况,为疫情流行趋势和防治措施提供依据。

方法

收集2021—2023年贵阳市新报告未接受抗病毒治疗的HIV-1感染者的血液样本及人口学信息。将获得的pol区基因序列上传到斯坦福大学HIV耐药数据库中进行基因型和耐药分析,基于最适基因距离(d=1.5%)构建分子传播网络并分析入网影响因素。

结果

共收集到171例样本,成功扩增获得有效序列123例(71.93%),发现6种基因型,以CRF07_BC(54.5%,67/123)和CRF01_AE(24.4%,30/123)为主,共有38条序列入网,入网率为30.89%,形成13个分子簇,簇内病例数在2~9例之间。多因素logistic回归结果显示,异性传播、CRF07_BC和CRF01_AE的感染者更容易入网(P<0.05)。重庆、广西、云南的CRF07_BC与贵阳市存在跨地区传播。123例样本的治疗前耐药率为17.07%(21/123),非核苷类逆转录酶抑制剂(NNRTIs)耐药率7.32%,核苷类逆转录酶抑制剂(NRTIs)耐药率3.25%,蛋白酶抑制剂(PI)耐药率3.25%,4例样本存在双重耐药。

结论

贵阳市新报告HIV-1感染者基因型以CRF07_BC和CRF01_AE为主,CRF07_BC与重庆、广西存在着紧密联系,HIV-1治疗前耐药率较高。今后应继续构建分子传播网络对该地区进行长期监测,与周边省市合作采取有效的艾滋病防控措施,进一步遏制病毒传播和蔓延。

1型艾滋病病毒  /  分子传播网络  /  基因型  /  耐药
Objective

To analyze the molecular transmission network characteristics and drug resistance of newly reported human immunodeficiency virus type 1 (HIV-1) infected individuals in Guiyang City, to provide a basis for epidemic trends and preventive and control measures.

Methods

Blood samples and demographic information of newly reported HIV-1 infected individuals who did not receive antiviral therapy in Guiyang City from 2021 to 2023 were collected. The obtained pol region gene sequences were uploaded to the Stanford University HIV drug resistance database for genotype and drug resistance analysis, and molecular transmission network was constructed based on the optimal gene distance (d=1.5%) and analyzed for factors influencing entry into the network.

Results

A total of 171 samples were collected, and 123 (71.93%) were successfully amplified to obtain valid sequences. Six genotypes were found, mainly CRF07_BC (54.5%, 67/123) and CRF01_AE (24.4%, 30/123). A total of 38 sequences were integrated into the network, with an integration rate of 30.89%. 13 molecular clusters were formed, and the number of cases in the clusters ranged from 2 to 9. Multivariate Logistic regression results showed that heterosexual transmission, CRF07_BC and CRF01_AE were more likely to enter the network(P<0.05). CRF07_BC in Chongqing, Guangxi, Yunnan and Guiyang had cross-regional transmission. The drug resistance rate of 123 samples before treatment was 17.07% (21/123), the drug resistance rates were 7.32% for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 3.25% for nucleoside reverse transcriptase inhibitors (NRTIs), 3.25% for protease inhibitors (PIs), and four samples showed dual drug resistance.

Conclusion

The genotypes of newly reported HIV-1 infected individuals in Guiyang were mainly CRF07_BC and CRF01_AE. CRF07_BC is closely related to Chongqing and Guangxi. The drug resistance rate of HIV-1 before treatment was high. In the future, we should continue to build molecular transmission networks for long-term monitoring of the area, cooperate with neighboring provinces and cities to take effective AIDS prevention and control measures to further curb the transmission and spread of the virus.

HIV-1  /  Molecular transmission network  /  Genotype  /  Drug resistance
申万敏, 王大朋, 蒋家俊, 简洁, 林瑞, 刘杨晶, 张羽, 佘敏, 张欐, 袁乡石, 龙世安, 马璐. 贵阳市123例新报告HIV-1感染者分子传播网络特征及耐药分析. 现代预防医学, 2025 , 52 (10) : 1902 -1908 . DOI: 10.20043/j.cnki.MPM.202412496
Wan-min SHEN, Da-peng WANG, Jia-jun JIANG, jie JIAN, Rui LIN, Yang-jing LIU, Yu ZHANG, Min SHE, Li ZHANG, Xiang-shi YUAN, Shi-an LONG, Lu MA. Molecular transmission network characteristics and drug resistance analysis of 123 newly reported HIV-1 cases, Guiyang City[J]. Modern Preventive Medicine, 2025 , 52 (10) : 1902 -1908 . DOI: 10.20043/j.cnki.MPM.202412496
近年来,随着分子流行病学的发展,利用HIV-1pol区基因序列的遗传相似性构建分子网络,可揭示HIV-1感染者的传播关系,结合其流行病学信息分析分子网络特征,为艾滋病精准干预和防控提供了有效的手段[1]。贵阳市是贵州省省会城市,是中国重要的生态休闲度假旅游城市,毗邻西部的云南省和华南的广西省,东部与华中湖南省相邻,北与四川、重庆接壤,都是艾滋病流行的重灾区,由于地理位置特殊且人口最为密集和流动最为频繁,为贵州省HIV流行和传播造成一定影响。目前针对贵州省HIV毒株有一定的研究与报道,但对HIV进行分子传播网络构建的较少,本研究构建分子传播网络是对贵阳市分子流行病学的一个进展,也是对贵阳市HIV-1传播关系的初步探索。因此本研究对象选取2021-2023年贵阳市新报告且未进行ART的HIV-1感染者,通过基因序列分析,了解该地区的流行毒株,构建分子传播网络并分析其特征和影响因素,识别重点区域和高危人群,为贵阳市乃至贵州省艾滋病疫情防控和多样性研究提供科学、全面的分子基线数据。
选取贵阳市疾病预防控制中心实验室2021年1月至2023年12月新报告且未接受抗病毒治疗的HIV-1感染者为研究对象。在研究对象签署知情同意后,共收集到血浆样本171例。通过“艾滋病综合防治信息填报系统”收集性别、年龄、户籍地、婚姻状况、民族、文化程度、现住址和感染途径人口学资料。本研究经贵阳市疾病预防控制中心伦理委员会批准(MR-52-25-012275)。
将储存于-80 ℃的HIV-1阳性血浆样本复溶,使用东北制药集团辽宁生物医药有限公司的人类免疫缺陷病毒核酸检测试剂盒,按照说明书标准操作规程从感染者血浆中提取出病毒RNA。参考文献[2],对pol基因序列(包括蛋白酶全长和反转录酶前300个氨基酸片段)进行PCR扩增。用1%琼脂糖凝胶电泳对PCR产物进行电泳,使用Illuminai Miseq测序仪对扩增阳性产物进行基因测序[3]
根据中国疾病预防控制中心发布的《全国艾滋病检测技术规范(2020年修订版)》[3],采用北京微未来病原微生物信息分析系统对测序数据进行整理、拼接和校正。将测序数据提交至斯坦福大学HIV耐药数据库(https://hivdb.stanford.edu/)分析基因型、耐药突变位点和耐药情况,其中耐药程度分为敏感(S),潜在耐药(P),低度耐药(L),中度耐药(I)和高度耐药(H),其中将后面3个耐药水平判定为耐药株。从HIV database下载重庆(47条)、云南(143条)、四川(251条)和广西(256条)4个邻省的参考序列,共697条序列,用IQ Tree1.6.12软件以最大似然法构建贵阳与4个邻省的系统进化树。
以CentOS 7平台配置HIV-TRACE程序所需的环境,采用Tamura-Nei93模型计算序列两两之间的基因距离,按照1.5%的基因阈值进行HIV-1分子传播网络的构建及可视化[4]。度是指一个节点与其他节点连接的数量,值越高传播风险越大。
使用SPSS 27.0进行数据分析。计数资料采用频数及构成比描述。采用单因素χ2检验和多因素logistic回归分析入网的影响因素。检验水准α=0.05。
本次研究共收集171例新报告HIV-1感染者,123例(71.93%)样本成功扩增获得pol基因序列。123名感染者以男性(93.5%,115/123)、≤25岁(40.7%,50/123)、本市(55.3%,68/123)、未婚(71.5%,88/123)、汉族(81.3%,100/123)、大专及以上文化程度(50.4%,62/123)、同性传播(74.0%,91/123)为主。共检测出6种基因型,包括CRF07_BC(54.5%,67/123)、CRF01_AE(24.4%,30/123)、URF(13.0%,16/123)、CRF55_01B(4.9%,6/123)、B(1.6%,2/123)和C(1.6%,2/123)。URF有B+C(11.4%,14/123)和B+CRF01_AE(1.6%,2/123)两种重组模式。见表1
基于1.5%基因距离阈值下,有38名感染者进入网络,入网率30.9%,形成13个分子簇和47条边,簇内节点数介于2~9个之间。5种亚型进入分子网络,其中CRF01_AE入网数量最多(15.4%,19/123),其次是CRF07_BC(8.9%,11/123)、URF(3.3%,4/123)、C(1.6%,2/123)和CRF55_01B(1.6%,2/123)。分子网络发现7个耐药株,感染途径均是同性传播。见图1
以是否进入分子网络作为因变量,χ2检验发现,年龄、户籍地、婚姻状况、文化程度、感染途径和毒株亚型入网危险差异均有统计学意义(P<0.05)。多因素logistic回归分析结果显示,与同性传播和URF相比,异性传播、CRF01_AE、CRF07_BC和其他亚型感染者更容易入网。
网络中有3个簇的节点数≥3,CRF01_AE构成最大的分子簇C1和C2。分子簇C1含9个节点,传播途径包含同性传播(11.1%,1/9)和异性传播(88.9%,8/9),异性传播里男性及≥50岁均占87.5%(7/8),文化程度均在初中及以下。分子簇C2发现2名≥50岁经非婚非商业异性传播的女性感染者。分子簇C1和C2均发现男同感染者与异性传播的男性和女性感染者相连,还发现异性传播感染者以≥50岁为主(92.3%,12/13)。分子簇C3由3名亚型为CRF07_BC的未婚MSM构成。见表2
构建的分子传播网络形成一个有91条序列的CRF07_BC分子簇,包含贵阳(19条)、重庆(8条)、云南(12条)和广西(52条)4个省份,来自重庆和广西序列与贵阳的关联度密切,其中重庆1条序列与贵阳序列连接的度达到了12,广西3条序列与贵阳连接的度在5以上;来自云南的序列与贵阳的关联度较低,与贵阳连接的度在3以下。网络中发现3个耐药株,其中SentosaBC-22_068对NRTIs-NNRTIs双重耐药,度为5,与云南、重庆、广西均有相连;SentosaBC-16_079对NRTIs耐药,度为1,与广西序列相连;SentosaBC-10_110对NNRTIs耐药,度为1,与重庆序列相连。见图2图3
123例样本中有32例检出耐药突变位点,其中21例样本判定为治疗前耐药,耐药率为17.07%(21/123)。NNRTIs为主要的突变类型,9例样本对NNRTIs单纯耐药(7.32%,9/123),NRTIs和PI单纯耐药各有4例样本(3.25%,4/123),NRTIs-NNRTIs双重耐药和PI-NNRTIs双重耐药各有2例样本。NNRTIs突变位点主要为E138G、E138K和K103N,NRTIs突变位点主要是M184I,PI突变位点以M46L较高。见表3
通过对贵阳市123例新发HIV-1感染者测序,发现6种HIV-1亚型,以CRF07_BC和CRF01_AE为主,与贵阳及国内其他地区的亚型流行情况类似[2,5-6]。本研究发现包含B+C和B+CRF01_AE两种重组模式的URF排第3位,其中B+C在URF占比最高,与孔令弘等人研究报告一致[7],而URF可能会增加流行重组型的形成[8],特别是近年来贵州省旅游业旺盛,交通便利及人口流动频繁,导致HIV毒株可能不断发生变异与重组,使基因型更加复杂,提示应加强对URF监测及对该亚型感染者进行更深的流行病学朔源调查。此外,研究还发现CRF55_01B、B和C的低流行毒株。
基于1.5%基因阈值下构建HIV-1分子传播网络,入网率为30.9%,形成13个分子簇。异性传播是影响研究对象入网的因素,可能与贵阳市及贵州省HIV以异性传播为主有关[9-10]。近年来,贵阳市新报告中老年HIV感染者/AIDS患者数呈逐年上升趋势,以异性传播为主[11]。本研究入网的异性传播感染者集中在≥50岁年龄段,以男性、低文化程度及非婚商业异性性行为为主,相关研究显示中老年人群感染与低档性暗娼有关[12-14],提示应加强与公安、社区等部门的协同联防联控工作力度,对茶室、低档浴室、街道洗脚店等重点场所加强宣传和干预,以及通过健康体检方式对中老年人进行艾滋病筛查,及时发现感染者并治疗。基因型是入网的影响因素之一,与四川彭州、重庆渝北、广西崇左、云南昆明研究结果相符[12,15-17]。入网的CRF01_AE形成4个分子簇,入网率高于其他亚型,可能与CRF01_AE具有较高的复制适应性和传播能力及较高的致病性有关[18]。入网的CRF07_BC主要见于年轻化的MSM人群,与既往研究类似[2]
有3个分子簇节点数≥3,分子簇C1和C2现住址主要分布在清镇市,入网率为59.8%(15/38),以往研究报道该地区为贵阳市≥50岁HIV/AIDS的高-高聚集区和热点区域,是大多数流动老年人选择居住地之一[11],而中老年感染者更有可能在本地区感染或传播HIV[19],本研究再次证明清镇市是贵阳市重点防控区域,需重点关注。同时,C1、C2两个簇主要以异性传播为主,但发现有男同感染者,且可能存在双性性行为[20],导致HIV传播链条更复杂。分子簇C2发现2名非婚非商业异性传播的女性感染者,而非婚非商业异性传播人群大多借助新媒体,隐匿性较强,干预难度大[21]。贵阳市是贵州省MSM人群最为集中、活跃度最高的地区,长期哨点监测显示MSM人群的HIV感染率较高[22],因此了解该人群HIV-1的分子网络具有重要意义。分子簇C3由3名亚型为CRF07_BC的MSM人群构成,同性传播形成的分子簇规模较小,可能与该人群的隐匿性特征、互联网及交通的便捷性为其提供了便利,跨地区传播导致不能构建完整的分子网络有关[23]
从贵阳市与周围省份HIV序列的分子传播和进化关系来看,重庆、云南、广西3个地区的序列与贵阳序列形成了一个CRF07_BC分子簇。在跨地区分子网络中发现重庆、广西与贵阳连接的度最大,说明来自重庆、广西的CRF07_BC与贵阳市的CRF07_BC有着紧密的传播关系,输入风险较大;云南的CRF07_BC与贵阳之间也存在传播关系,相较重庆和广西,与贵阳的传播关系较小,输入风险较小。本研究123例样本的治疗前耐药率为17.07%,高于既往研究[10,24],也高于国内其他地区[14,20],耐药率处于WHO耐药警戒线的中上度流行水平,说明贵阳市治疗前耐药情况较严重。跨地区分子网络中发现3个耐药株,与重庆、云南、广西序列相连,提示贵阳市耐药株与重庆、云南、广西可能存在关联,今后需加强耐药监测力度,减少外来耐药毒株在本地传播。同时,在进化树发现贵阳的部分序列与云南、广西、重庆有较近的分支汇聚,表明这些地区的部分HIV序列亲缘关系相对较近,证明这些地区在HIV传播和进化上存在一定关联。
综上所述,贵阳市HIV-1感染者耐药率较高,异性传播、CRF07_BC和CRF01_AE为贵阳市HIV-1分子传播网络的入网影响因素。重庆、广西、云南和贵阳存在CRF07_BC较大的输入风险。提示今后贵阳市艾滋病防控工作应充分利用分子传播网络,加强贵阳市HIV患者抗病毒治疗前耐药监测,并在重点区域和重点人群加强开展健康教育的工作,提高人群艾滋病预防及检测意识,同时强化与周边省份的协同防控合作,推动各地区间防控信息及HIV病毒基因序列的共享,达到对艾滋病的精准防控。回顾本文研究,由于招募到的研究样本数量较少,研究人群类别太单一,分析结论存在不足,存在一定的局限性。
  • 贵州省卫生健康委科学技术基金项目[贵州省2021年度科学技术基金项目(2021)](gzwkj2021-435)
  • 应用分子传播网络探讨贵阳市新发HIV/AIDS病例HIV1基因分型及传播特征(gzwkj2021-435)
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doi: 10.20043/j.cnki.MPM.202412496
  • 接收时间:2024-12-27
  • 首发时间:2026-03-18
  • 出版时间:2025-05-25
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  • 收稿日期:2024-12-27
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贵州省卫生健康委科学技术基金项目[贵州省2021年度科学技术基金项目(2021)](gzwkj2021-435)
应用分子传播网络探讨贵阳市新发HIV/AIDS病例HIV1基因分型及传播特征(gzwkj2021-435)
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    1.贵州医科大学公共卫生与健康学院,贵州 贵阳 550025
    2.贵阳市疾病预防控制中心

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
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