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Article(id=1240950909329526835, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240950898113966774, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202312010, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1701360000000, receivedDateStr=2023-12-01, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773795352536, onlineDateStr=2026-03-18, pubDate=1712678400000, pubDateStr=2024-04-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773795352536, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773795352536, creator=13701087609, updateTime=1773795352536, updator=13701087609, issue=Issue{id=1240950898113966774, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='7', pageStart='1153', pageEnd='1344', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773795349862, creator=13701087609, updateTime=1773795519367, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1240951609136567133, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240950898113966774, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1240951609136567134, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240950898113966774, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1302, endPage=1307, ext={EN=ArticleExt(id=1240950910642344084, articleId=1240950909329526835, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Study on gene subtypes and molecular transmission characteristics of newly reported HIV-1 infection in Luzhou city, columnId=1228016573156360233, journalTitle=Modern Preventive Medicine, columnName=Disease Control and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the transmission of HIV-1 infections newly found in Luzhou city, Sichuan Province in 2021,and to investigate the risk factors and characteristics of HIV-1 transmission network, so as to provide data for the prevention and control of AIDS epidemic in Luzhou.

Methods

The blood samples and demographic information of 363 newly reported HIV-1 infections in Luzhou in 2021 were collected. The HIV-1 pol gene sequence was amplified by nested PCR, and the virus subtype and transmissible drug resistance were analyzed according to the pol gene sequence. The molecular network was constructed based on the optimal gene distance (d=1.5%) and the characteristics of molecular transmission network and its influencing factors were analyzed.

Results

A total of 346 valid sequences were obtained, including 113 cases of CRF07_BC subtype (32.66%),107 cases of CRF01_AE subtype (30.92%), 99 cases of CRF08_BC subtype (28.61%), 18 cases of CRF105_0108 subtype (5.20%), and 9 cases of other subtypes (2.60%). The rate of transmitted drug resistance of HIV-1 was 15.03% (52/346), and dual drug resistance was detected in 4 samples. A total of 34 molecular clusters were formed, and the number of cases in the clusters ranged from 2 to 25, with 148 individuals (42.77%) included in the transmission network under the optimal genetic distance threshold (1.5%). There were significant differences in age, education level, infection route, genotype, and registered residence registration (P<0.05). Logistic regression found that education level and registered residence were the influencing factors of network access.

Conclusion

The newly reported HIV-1 infection in Luzhou city shows diversity of virus genes. CRF01_AE,CRF07_BC, and CRF08_ BC subtype have become the main subtype of epidemic virus strains, and molecular transmission network should be established for long-term monitoring in this region to take targeted measures to block its further transmission.

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目的

分析四川省泸州市2021年新发现人类免疫缺陷病毒（human immunodeficiency virus, HIV）感染者传播情况，了解HIV-1传播网络的危险因素和特点，为本地区艾滋病疫情防控提供数据。

方法

收集2021年363份泸州市新报告的HIV-1感染者血样及人口学信息。通过巢式PCR扩增HIV-1 pol区基因序列，根据pol区基因序列进行病毒亚型和传播性耐药分析，基于最适基因距离（d=1.5%）构建分子网络，分析分子传播网络特征及其影响因素。

结果

共获得有效序列346份，包括CRF07_BC亚型113例（32.66%），CRF01_AE亚型107例（30.92%），CRF08_BC亚型99例（28.61%），CRF105_0108亚型18例（5.20%），其他亚型9例（2.60%）。HIV-1传播性耐药率为15.03%（52/346），4份样本检出双重耐药。以1.5%作为基因阈值构建分子传播网络，共形成34个分子簇，簇内病例数分别在2 ~ 25例，入网病例148例，入网率为42.77%。不同年龄、文化程度、感染途径、基因亚型和户籍入网差异有统计学意义（P<0.05）。Logistic回归发现文化程度、户籍为入网的影响因素。

结论

泸州市新报告HIV-1感染者病毒基因呈现多样性。CRF01_AE、CRF07_BC和CRF08_BC亚型是主要流行毒株亚型，应构建分子传播网络对该地区进行长期监测，采取针对性的措施阻断疫情进一步传播。

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陈航，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=C7qJp5mooTRCBxBkvv8dfA==, magXml=0sGuuIVmyt5Tz36/RXzCcw==, pdfUrl=null, pdf=XIrvpWWM/3R0DE07AJQa/w==, pdfFileSize=1199884, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=j49LncCXKfq+2h9qXqVAbw==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=6MeJkbiifhu43D4YQGEfbQ==, mapNumber=null, authorCompany=null, fund=null, authors=

苟钊（1974—），男，本科，副主任中医师，研究方向：临床医学治疗，公共卫生方面的研究和管理

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苟钊（1974—），男，本科，副主任中医师，研究方向：临床医学治疗，公共卫生方面的研究和管理

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苟钊（1974—），男，本科，副主任中医师，研究方向：临床医学治疗，公共卫生方面的研究和管理

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Analysis on drug resistance in patients over 50 years old who failed with HIV antiviral treatment in Luzhou City[J].Journal of Preventive Medicine Information, 2023, 39(10): 1230-1233., articleTitle=Analysis on drug resistance in patients over 50 years old who failed with HIV antiviral treatment in Luzhou City, refAbstract=null), Reference(id=1240972180515778677, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, doi=null, pmid=null, pmcid=null, year=2021, volume=13, issue=5, pageStart=879, pageEnd=null, url=null, language=null, rfNumber=[23], rfOrder=34, authorNames=Rhee SY, Tzou PL, Shafer RW, journalName=Viruses, refType=null, unstructuredReference=Rhee SY, Tzou PL, Shafer RW. Temporal trends in HIV-1 mutations used for the surveillance of transmitted drug resistance[J].Viruses, 2021, 13(5): 879., articleTitle=Temporal trends in HIV-1 mutations used for the surveillance of transmitted drug resistance, refAbstract=null), Reference(id=1240972180595470459, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, doi=null, pmid=null, pmcid=null, year=2022, volume=74, issue=6, pageStart=1055, pageEnd=1062, url=null, language=null, rfNumber=[24], rfOrder=35, authorNames=Mcclung RP, Osteram, Ocfemia M, journalName=Clinical Infectious Diseases, refType=null, unstructuredReference=Mcclung RP, Osteram, Ocfemia M, et al. Transmitted drug resistance among human immunodeficiency virus(HIV)-1 diagnoses in the United States,2014-2018[JJ[J]. Clinical Infectious Diseases,2022, 74(6): 1055-1062., articleTitle=Transmitted drug resistance among human immunodeficiency virus(HIV)-1 diagnoses in the United States,2014-2018, refAbstract=null), Reference(id=1240972180691939454, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, doi=null, pmid=null, pmcid=null, year=2012, volume=null, issue=2, pageStart=371, pageEnd=null, url=null, language=null, rfNumber=[25], rfOrder=36, authorNames=Castellano C, Pastor-Satorras R, journalName=Scientific Reports, refType=null, unstructuredReference=Castellano C, Pastor-Satorras R. Competing activation mechanisms in epidemics on networks[J]. Scientific Reports, 2012,(2): 371., articleTitle=Competing activation mechanisms in epidemics on networks, refAbstract=null)], funds=[Fund(id=1240972173268022179, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, awardId=川大-泸州人文社科（2022, language=CN, fundingSource=2022年度四川大学-泸州市人民政府战略合作项目(川大-泸州人文社科（2022), fundOrder=null, country=null), Fund(id=1240972173406434220, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, awardId=2022CDLZ-22, language=CN, fundingSource=HIV新发感染者的CD4变化规律及影响因素研究(2022CDLZ-22), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1240972164476760477, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, xref=null, ext=[AuthorCompanyExt(id=1240972164497732000, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, companyId=1240972164476760477, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Luzhou Center for Disease Control and Prevention, Luzhou, Sichuan 646000, China), AuthorCompanyExt(id=1240972164506120609, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, companyId=1240972164476760477, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=泸州市疾病预防控制中心，四川 泸州 646000)])], figs=[ArticleFig(id=1240972172034896723, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, language=EN, label=Figure 1, caption=HIV-1 pol region phylogenetic tree, figureFileSmall=jo9+jnP0FXg1jaWzKpsqVA==, figureFileBig=lKwfyJFT0BjknP+8LDWgCw==, tableContent=null), ArticleFig(id=1240972172177503064, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, language=CN, label=图1, caption=HIV-1pol区系统进化树, figureFileSmall=jo9+jnP0FXg1jaWzKpsqVA==, figureFileBig=lKwfyJFT0BjknP+8LDWgCw==, tableContent=null), ArticleFig(id=1240972172286554977, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, language=EN, label=Figure 2, caption=Molecular network propagation characteristics, figureFileSmall=jou0GlRKETAk/t/s2F+sgA==, figureFileBig=u75H4cgRrPE9L/egvz+/zA==, tableContent=null), ArticleFig(id=1240972172362052457, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, language=CN, label=图2, caption=分子网络传播特征图, figureFileSmall=jou0GlRKETAk/t/s2F+sgA==, figureFileBig=u75H4cgRrPE9L/egvz+/zA==, tableContent=null), ArticleFig(id=1240972172475298675, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, language=EN, label=Table 1, caption=

Analysis of the molecular transmission network and risk factors for newly reported HIV/AIDS in Luzhou city, Sichuan Province in 2021

, figureFileSmall=null, figureFileBig=null, tableContent=
变 量例数［n（%）］入网例数［n（%）］单因素分析多因素分析
χ2值P值aOR值（95%CI）P值
性别2.9130.088
男216（62.43）100 (46.29)
女130（37.57）48（36.92）
年龄（岁）14.8710.001
<5051（14.74）13（25.49）
50～69213（61.56）87（40.85）
≥7082（23.70）48（58.54）
文化程度20.496a<0.001a
文盲59（17.05）37（62.71）1
小学221（63.87）89（40.27）0.455（0.249～0.833）0.0106
初中43（12.43）17（39.53）0.421（0.187～0.951）0.0370
高中（中专）以上19（5.49）2（10.53）0.103（0.031～0.346）0.0002
不详4（1.16）3（75.00）
婚姻状况1.032a0.811a
未婚44（12.72）16（36.36）
已婚/有配偶202（58.38）88（43.56）
离异/丧偶94（27.17）41（43.62）
不详6（1.73）3（50.00）
职业1.2140.545
农民269（77.75）116（43.12）
家务及待业45（13.00）21（46.67）
其它32（9.25）11（34.38）
感染途径9.658a0.021a
商业性性行为227（65.61）110（48.46）
临时性伴92（26.59）30（32.61）
配偶或固定性伴16（4.62）6（37.50）
其它11（3.18）2（18.18）
基因亚型17.116a0.001a
CRF01_AE107（30.92）52（48.60）
CRF07_BC113（32.66）55（48.67）
CRF08_BC99（28.61）31（31.31）
CRF105_010818（5.20）10（55.56）
其它亚型b9（2.60）0（0.00）
户籍24.6900.001
江阳区55（15.90）33（60.00）1
龙马潭区26（7.51）17（65.38）1.199（0.437～3.292）0.725
纳溪区28（8.09）14（50.00）0.548 (0.211～1.428)0.218
合江县87（25.14）37（42.53）0.436（0.212～0.897）0.024
泸县60（17.34）23（38.33）0.369（0.169～0.809）0.013
古蔺县32（9.25）6（18.75）0.119（0.040～0.358）<0.001
叙永县46（13.29）13（28.26）0.223（0.093～0.534）0.001
市外12（3.47）5（41.67）0.346（0.081～1.484）0.153
非婚性行为人数（人）2.0240.363
026（7.51）8（30.77）
1～2157（45.38）66（42.04）
>2163（47.11）74（45.40）
), ArticleFig(id=1240972172592739196, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, language=CN, label=表1, caption=

四川省泸州市2021年新报告HIV/AIDS感染者分子传播网络及入网危险因素分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变 量例数［n（%）］入网例数［n（%）］单因素分析多因素分析
χ2值P值aOR值（95%CI）P值
性别2.9130.088
男216（62.43）100 (46.29)
女130（37.57）48（36.92）
年龄（岁）14.8710.001
<5051（14.74）13（25.49）
50～69213（61.56）87（40.85）
≥7082（23.70）48（58.54）
文化程度20.496a<0.001a
文盲59（17.05）37（62.71）1
小学221（63.87）89（40.27）0.455（0.249～0.833）0.0106
初中43（12.43）17（39.53）0.421（0.187～0.951）0.0370
高中（中专）以上19（5.49）2（10.53）0.103（0.031～0.346）0.0002
不详4（1.16）3（75.00）
婚姻状况1.032a0.811a
未婚44（12.72）16（36.36）
已婚/有配偶202（58.38）88（43.56）
离异/丧偶94（27.17）41（43.62）
不详6（1.73）3（50.00）
职业1.2140.545
农民269（77.75）116（43.12）
家务及待业45（13.00）21（46.67）
其它32（9.25）11（34.38）
感染途径9.658a0.021a
商业性性行为227（65.61）110（48.46）
临时性伴92（26.59）30（32.61）
配偶或固定性伴16（4.62）6（37.50）
其它11（3.18）2（18.18）
基因亚型17.116a0.001a
CRF01_AE107（30.92）52（48.60）
CRF07_BC113（32.66）55（48.67）
CRF08_BC99（28.61）31（31.31）
CRF105_010818（5.20）10（55.56）
其它亚型b9（2.60）0（0.00）
户籍24.6900.001
江阳区55（15.90）33（60.00）1
龙马潭区26（7.51）17（65.38）1.199（0.437～3.292）0.725
纳溪区28（8.09）14（50.00）0.548 (0.211～1.428)0.218
合江县87（25.14）37（42.53）0.436（0.212～0.897）0.024
泸县60（17.34）23（38.33）0.369（0.169～0.809）0.013
古蔺县32（9.25）6（18.75）0.119（0.040～0.358）<0.001
叙永县46（13.29）13（28.26）0.223（0.093～0.534）0.001
市外12（3.47）5（41.67）0.346（0.081～1.484）0.153
非婚性行为人数（人）2.0240.363
026（7.51）8（30.77）
1～2157（45.38）66（42.04）
>2163（47.11）74（45.40）
), ArticleFig(id=1240972172756317063, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, language=EN, label=Table 2, caption=

Analysis of HIV-1 transmissible genotype resistance mutation sites in Luzhou city

, figureFileSmall=null, figureFileBig=null, tableContent=
突变位点类型基因突变位点突变数（例）
PI突变5
M46L2
I47V1
L24F1
T74P1
NRTI突变21
M184I/V5
M41L4
D67G/N3
K70E/N3
T215A/S3
A62V1
K65R1
S68N1
NNRTI突变47
K103N/Q13
E138A/G12
V179D/E/L/T5
V106I/M4
K101E4
G190A4
P225H2
F227L2
Y181C1
), ArticleFig(id=1240972172953449363, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240950909329526835, language=CN, label=表2, caption=

泸州市HIV-1传播性基因型耐药突变位点情况*

, figureFileSmall=null, figureFileBig=null, tableContent=
突变位点类型基因突变位点突变数（例）
PI突变5
M46L2
I47V1
L24F1
T74P1
NRTI突变21
M184I/V5
M41L4
D67G/N3
K70E/N3
T215A/S3
A62V1
K65R1
S68N1
NNRTI突变47
K103N/Q13
E138A/G12
V179D/E/L/T5
V106I/M4
K101E4
G190A4
P225H2
F227L2
Y181C1
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泸州市新报告HIV-1感染者基因亚型及分子传播特征研究
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苟钊 , 艾雨 , 许文平 , 陈航 , 余明 , 肖体呈 , 刘小红
现代预防医学 | 疾病预防控制 2024,51(7): 1302-1307
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现代预防医学 | 疾病预防控制 2024, 51(7): 1302-1307
泸州市新报告HIV-1感染者基因亚型及分子传播特征研究
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苟钊, 艾雨, 许文平, 陈航 , 余明, 肖体呈, 刘小红
作者信息
  • 泸州市疾病预防控制中心，四川 泸州 646000

    • 苟钊（1974—），男，本科，副主任中医师，研究方向：临床医学治疗，公共卫生方面的研究和管理

通讯作者:

陈航，E-mail:
Study on gene subtypes and molecular transmission characteristics of newly reported HIV-1 infection in Luzhou city
Zhao GOU, Yu AI, Wen-ping XU, Hang CHEN , Ming YU, Ti-cheng XIAO, Xiao-hong LIU
Affiliations
  • Luzhou Center for Disease Control and Prevention, Luzhou, Sichuan 646000, China
出版时间: 2024-04-10 doi: 10.20043/j.cnki.MPM.202312010
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摘要
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目的

分析四川省泸州市2021年新发现人类免疫缺陷病毒（human immunodeficiency virus, HIV）感染者传播情况，了解HIV-1传播网络的危险因素和特点，为本地区艾滋病疫情防控提供数据。

方法

收集2021年363份泸州市新报告的HIV-1感染者血样及人口学信息。通过巢式PCR扩增HIV-1 pol区基因序列，根据pol区基因序列进行病毒亚型和传播性耐药分析，基于最适基因距离（d=1.5%）构建分子网络，分析分子传播网络特征及其影响因素。

结果

共获得有效序列346份，包括CRF07_BC亚型113例（32.66%），CRF01_AE亚型107例（30.92%），CRF08_BC亚型99例（28.61%），CRF105_0108亚型18例（5.20%），其他亚型9例（2.60%）。HIV-1传播性耐药率为15.03%（52/346），4份样本检出双重耐药。以1.5%作为基因阈值构建分子传播网络，共形成34个分子簇，簇内病例数分别在2 ~ 25例，入网病例148例，入网率为42.77%。不同年龄、文化程度、感染途径、基因亚型和户籍入网差异有统计学意义（P<0.05）。Logistic回归发现文化程度、户籍为入网的影响因素。

结论

泸州市新报告HIV-1感染者病毒基因呈现多样性。CRF01_AE、CRF07_BC和CRF08_BC亚型是主要流行毒株亚型，应构建分子传播网络对该地区进行长期监测，采取针对性的措施阻断疫情进一步传播。

艾滋病病毒  /  耐药  /  分子传播网络  /  基因亚型  /  传播特征
Objective

To analyze the transmission of HIV-1 infections newly found in Luzhou city, Sichuan Province in 2021,and to investigate the risk factors and characteristics of HIV-1 transmission network, so as to provide data for the prevention and control of AIDS epidemic in Luzhou.

Methods

The blood samples and demographic information of 363 newly reported HIV-1 infections in Luzhou in 2021 were collected. The HIV-1 pol gene sequence was amplified by nested PCR, and the virus subtype and transmissible drug resistance were analyzed according to the pol gene sequence. The molecular network was constructed based on the optimal gene distance (d=1.5%) and the characteristics of molecular transmission network and its influencing factors were analyzed.

Results

A total of 346 valid sequences were obtained, including 113 cases of CRF07_BC subtype (32.66%),107 cases of CRF01_AE subtype (30.92%), 99 cases of CRF08_BC subtype (28.61%), 18 cases of CRF105_0108 subtype (5.20%), and 9 cases of other subtypes (2.60%). The rate of transmitted drug resistance of HIV-1 was 15.03% (52/346), and dual drug resistance was detected in 4 samples. A total of 34 molecular clusters were formed, and the number of cases in the clusters ranged from 2 to 25, with 148 individuals (42.77%) included in the transmission network under the optimal genetic distance threshold (1.5%). There were significant differences in age, education level, infection route, genotype, and registered residence registration (P<0.05). Logistic regression found that education level and registered residence were the influencing factors of network access.

Conclusion

The newly reported HIV-1 infection in Luzhou city shows diversity of virus genes. CRF01_AE,CRF07_BC, and CRF08_ BC subtype have become the main subtype of epidemic virus strains, and molecular transmission network should be established for long-term monitoring in this region to take targeted measures to block its further transmission.

AIDS virus  /  Drug resistance  /  Molecular transmission network  /  Gene subtype  /  Propagation characteristics
苟钊, 艾雨, 许文平, 陈航, 余明, 肖体呈, 刘小红. 泸州市新报告HIV-1感染者基因亚型及分子传播特征研究. 现代预防医学, 2024 , 51 (7) : 1302 -1307 . DOI: 10.20043/j.cnki.MPM.202312010
Zhao GOU, Yu AI, Wen-ping XU, Hang CHEN, Ming YU, Ti-cheng XIAO, Xiao-hong LIU. Study on gene subtypes and molecular transmission characteristics of newly reported HIV-1 infection in Luzhou city[J]. Modern Preventive Medicine, 2024 , 51 (7) : 1302 -1307 . DOI: 10.20043/j.cnki.MPM.202312010
正文
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人类免疫缺陷病毒（human immunodeficiency virus, HIV）是一个重大的全球公共卫生问题，迄今已夺去4 040万人的生命，一些国家报告的新发感染呈上升趋势[1]。1987年2月，我国诊断出大陆首例艾滋病（acquired immune deficiency syndrome, AIDS）患者以来，截至2020年底，中国有约105万HIV/AIDS感染者，累积死亡人数35万。泸州市自1996年发现首例本土HIV感染病例，报告病例数呈逐年上升趋势。泸州市地处川渝滇黔结合部，地理环境错综复杂，人口流动性大，HIV流行因素复杂，这给AIDS预防控制工作带来了巨大挑战[2]。
HIV分子传播网络分析结合社会网络分析是利用病毒基因序列研究传染病传播特征的新兴技术，全球已经有大量的研究将该技术应用于HIV疫情监测、发掘传播关系、传播簇、传播关键节点和传播热点等[3-5]。该技术成为研究AIDS传播规律的重要手段，做到精准干预及效果评估，降低新发感染率及HIV传播具有重要的意义[4,6]。2017年3月，美国CDC在全球首次发布《HIV分子传播簇鉴定、调查及对策指南》。中国CDC于2019年9月牵头发布《HIV传播网络监测和干预技术指南》（试行），四川省作为监测和干预试点之一，分子传播网络分析对防控AIDS疫情以及分子传播重点簇监测发挥了重要作用，根据2019年的数据显示，新增AIDS患者，性传播感染得AIDS的比例高达96.7%，其中异性性传播占比73.7%。本研究结合流行病学调查，分析HIV/AIDS感染者之间分子网络关系及相关影响因素，掌握传播簇内病例特征、识别出高风险传播者，为泸州及周边地区AIDS精准防控提供科学依据。
1　对象和方法
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1.1　对象
1.1.1　样本来源
收集2019—2021年泸州市新确诊的HIV/AIDS感染者样本363例。本研究获得泸州市疾病预防控制中心伦理委员会批准（批准号为：LZCDC/LS-2023003）。
1.1.2　信息来源
样本信息转自中国疾病预防控制中心AIDS综合防治信息系统。
1.2　方法
1.2.1　核酸提取和pol区基因扩增
测序参照《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[7]。
1.2.2　基因亚型及耐药分析
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进行分型鉴定。基因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/测序成功的样本数×100%。
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），以d≤1.5%判定传播网络[5,8]。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；高危风险传播者的度值≥12，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　构建系统进化树
以美国LosAlamos国家实验室HIV数据库各亚型为参考株，应用BioEdit软件进行比对和校正，使用MEGA-X软件Kimura 2参数模型(Bootstrap =1 000)构建邻接法系统进化树[9]。
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
363例样本全部进行pol区基因扩增，成功获得pol区基因序列346条，扩增成功率为95.32%（346/363）。以男性、50～70岁、小学及以下文化程度、已婚/有配偶、农民、商业性性行为传播途径为主，分别占62.43%、61.56%、80.92%、58.38%、77.75%、65.61%。户籍为泸州市334例（96.53%），市外12例（3.47%）。非婚性伴人数为0人、1～2人、2人以上分别有26人(7.51% )、157人（45.38%）、163人（47.11%）。见表1。
2.2　基因进化树分型
346例样品中，CRF07_BC亚型113例（32.66%），CRF01_AE亚型107例（30.92%），CRF08_BC亚型99例（28.61%），CRF105_0108亚型18例（5.20%），其他亚型8例（2.60%）。见图1。
2.3　HIV-1传播性基因型耐药分析
346例样本中共有91份样本检出耐药突变位点，其中52份样本判定为耐药，耐药率为15.03%（52/346）。耐药样本共检出73个耐药突变位点，非核苷类逆转录酶抑制剂（non-nucleoside reverse transcriptase inhibitors,NNRTI）突变为主要的突变类型，占64.38%（47/73），其次核苷类逆转录酶抑制剂（nucleoside reverse transcriptase inhibitors, NRTI）突变占28.77%（21/73）、蛋白酶抑制剂（protease inhibitors, PI）突变占6.85%（5/73）。NNRTI突变主要为K103N/Q和E138A/G，分别占27.66%（13/47）、25.53%（12/47），NRTI突变主要是M184I/V和M41L，分别占23.81%（5/21）、19.05%（4/21），具体突变位点见表2。4份样本检出双重耐药，其中3份样本对NRTI和NNRTI双重耐药，1份样本表现对PI和NRTI的双重耐药。
2.4　HIV-1分子网络传播特征
148个病例进入分子传播网络（d≤1.5%），形成34个传播簇，总体入网率42.77%（148/346）。CRF01_AE、CRF07_BC、CRF08_BC和CRF105_0108的入网率分别为48.60%（52/107）、48.67%（55/113）、31.31%（31/99），55.56%（10/18）。传播簇节点的M（P25，P75）为2（2，4），节点度值的M（P25，P75）为3（1，6），43个节点（29.05%）只有1个潜在的传播同伴。本研究中节点>2的传播簇有16个，其中最大的传播簇含有25个节点，由CRF01_AE亚型形成；其次为CRF07_BC亚型形成含有22个节点的大簇。CRF105_0108形成了一个包含8个节点的传播簇。见图2。
2.5　入围危险因素分析
单因素方面，年龄、文化程度、感染途径、基因亚型和户籍入网危险差异均有统计学意义（P<0.05）；性别、婚姻状况、职业和非婚性行为人数组的入网危险的差异均无统计学意义（P>0.05）。采用前进（有条件）法构建二元logistic回归模型显示：文化程度和户籍是入网的影响因素，文化程度为文盲和户籍为江阳区为入网的危险因素。见表1。
3　讨论
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本研究通过分析泸州市HIV/AIDS感染者之间分子网络特性，结合2019—2021年间疫情中重点街道和人群特征，对疫情精准防控和干预发挥着重要作用。纳入346病例中共发现5种HIV-1亚型，构成主要以CRF07_BC、CRF01_AE和CRF08_BC三种亚型为主，分别占32.66%、30.92%、28.61%，与我国及四川省既往研究结果相一致[5,10-13]。但是CRF08_BC的占比明显提高，高于四川既往流行病学调查显示的结果（<10%）[11]，也远远高于2015年第4次全国HIV分子流行病学调查结果（11.3%）[3]。
泸州市CRF08_BC（28.61%）占比提升，和CRF07_BC、CRF01_AE两种亚型占比相近已成为优势毒株，CRF07_BC和CRF08_BC亚型均以异性传播感染为主。研究显示，CRF07_BC和CRF08_BC具有共同的重组祖先毒株，均以C亚型病毒为骨架，而后分别经过了各自独立的重组过程而产生[14-16]，推测CRF08_BC和CRF07_BC两种关系密切。CRF07_BC和CRF08_BC最初均是从静脉吸毒人群（IDU）中被发现，随着社会的变迁已通过性传播途径在普通人群中流行[14]。本研究中CRF08_BC亚型传播簇和CRF01_AE均为11个，比CRF07_BC传播簇多，说明CRF08_BC亚型基因存在多样性，形成更多个传播簇，也说明CRF08_BC亚型在泸州流行传播是近期事件，需要进一步通过分子溯源手段对CRF08_BC亚型病例感染源头与途径进行进一步跟踪。CRF01_AE的分子传播簇和关联程度相较于CRF07_BC和CRF08_BC大，说明CRF01_AE在分子传播网络内存在的推断传播关系更多，传播风险更高。CRF07_BC亚型内形成CRF07_BC_1（22病例，83边）和CRF07_BC_2（11病例，25边）两个仅次于CRF01_AE_1（25病例，233边）大的传播簇，表明CRF07_BC亚型传播风险高。CRF105_0108亚型是近年四川省发现的新亚型[17]，本研究发现其形成了一个较大的传播簇（8病例，18边），提示其存在快速传播风险。根据以上数据，结合病例的户籍及住址，可以分析得出CRF07_BC、CRF08_BC、CRF01_AE所在的病例集中区域为泸州市HIV防控的重点区域，这些区域主要为人口密集、外来及流动人口多等特征，这些特征决定了重点区域的流行病防控难度大。
本研究发现泸州市HIV-1治疗前耐药率为15.03%，高于安徽阜阳、浙江绍兴、甘肃等地[18-20]，低于凉山州某县[21]。主要为NNRTIs耐药，其中K103N/Q占比高，与早前该地区研究一致[22]，该位点突变也是最常见的传播性耐药突变[23-24]。2018年一项调查显示该地的治疗前耐药率仅为9.7%[10]，说明近年来泸州市治疗前耐药形势愈发严峻，提示需要进一步加强干预防止耐药基因的快速传播。
在分子传播簇中，节点的度值可以反映出个体的传播风险，度值越高，传播风险越大[25]。本研究中度值≥12的HIV/AIDS感染者有23例，共拥有512个度，最大度值24；而传播簇CRF01_AE_1，由25个病例构成，共拥有466个度，有22个成员度值≥12且其中7名为最高值24，特别是入网感染者2019QR1463、2019QR2351、2020QR1059和2020QR1429。根据流行病学调查，曾从事暗娼活动，表明她们可能在泸州HIV-1传播中相对活跃，是重要的防控对象。暗娼场所具有数量较大、分散隐蔽、无固定场所、流动性强等特点，使得暗娼作为传播纽带是AIDS传播阻断的关键人群，若能对其实施精准防控、将能够有效降低继发的传播感染。同时，暗示传播簇CRF01_AE_1已成为泸州地区热点、关注HIV-1传播链，需进行重点动态监测。结合传播热点和上述的重点区域，我们可以确定泸州市HIV传染的重点人群教育水平低，初中及以下教育的感染病例高达93.35%；其次，重点人群的年龄较大，≥50岁占比85.26%，农民（77.75%）为主要群体、非婚商业性行为传播途径（65.61%）为主；以上数据，可以刻画出重点人群文化水平低、经济收入一般，对于传染性疾病预防认识不足的特征。
结合重点区域及重点人群的特征，我们可以提出针对泸州HIV防控的几点建议：（1）根据划定的重点区域，与当地公安部门联合行动，从根本上肃清暗娼活动，阻断传播链。（2）在重点区域内，对符合重点人群特征的群体，进行针对性的HIV科普活动。该群体的知识文化水平低、年龄大，形式上，要多以图片、短视频等方式科普；内容上，少讲理论，多讲疾病的危害，多以案例展示。（3）同时要发动重点区域的社区及重点人群的家属，持续关注和加强HIV传染性及危害的宣讲，建立反馈途径，及时收集基层工作开展遇到的问题。
综上所述，泸州市新报告HIV/AIDS人群HIV-1亚型以CRF01_AE、CRF07_BC和CRF08_BC为主，泸州地区地理、文化环境、经济发展等特性可能是CRF07_BC和CRF08_BC传播途径转变的重要因素。泸州市新报告病例传播簇中存在传播活跃者，提示下一步应充分利用分子传播网络技术，并结合流行病学资料，明确HIV-1流行的重点区域和重点人群特征，提出适合泸州本地疫情特征的控制HIV-1传播的精准防治策略，控制疫情进一步蔓延。
基金
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  • 2022年度四川大学-泸州市人民政府战略合作项目(川大-泸州人文社科（2022)
  • HIV新发感染者的CD4变化规律及影响因素研究(2022CDLZ-22)
文献
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2024年第51卷第7期
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doi: 10.20043/j.cnki.MPM.202312010
  • 接收时间：2023-12-01
  • 首发时间：2026-03-18
  • 出版时间：2024-04-10
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  • 收稿日期：2023-12-01
基金
2022年度四川大学-泸州市人民政府战略合作项目(川大-泸州人文社科（2022)
HIV新发感染者的CD4变化规律及影响因素研究(2022CDLZ-22)
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    泸州市疾病预防控制中心，四川 泸州 646000

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