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Article(id=1323941343294271641, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1323941237702668764, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202502190, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1739376000000, receivedDateStr=2025-02-13, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793581813882, onlineDateStr=2026-11-02, pubDate=1765296000000, pubDateStr=2025-12-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793581813882, onlineIssueDateStr=2026-11-02, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793581813882, creator=13701087609, updateTime=1793581813882, updator=13701087609, issue=Issue{id=1323941237702668764, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='23', pageStart='4225', pageEnd='4416', issueExtLink='null', onlineDate='null', pubDate='1765296000000', pubDateStr='2025-12-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793581788707, creator='13701087609', updateTime=1793581887795, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1323941653374959780, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1323941237702668764, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1323941653374959781, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1323941237702668764, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=4396, endPage=4402, ext={EN=ArticleExt(id=1323941344925855898, articleId=1323941343294271641, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Drug resistance and molecular network characteristics among HIV/AIDS patients with treatment failure in Urumqi City, columnId=1228016573156360233, journalTitle=Modern Preventive Medicine, columnName=Disease Control and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the drug resistance and molecular network characteristics of HIV/AIDS treatment failure patients in Urumqi City, and provide a theoretical basis for AIDS prevention and control.

Methods

A total of 1 281 patients who received antiviral treatment in AIDS antiviral designated medical institutions in Urumqi City from 2018 to 2023 and had a viral load (VL) ≥1 000 copies/mL were classified as treatment failure patients and included. The pol region gene of HIV-1 was amplified by nested PCR, and a phylogenetic tree was constructed using the neighbor-joining method. χ2 text and logistic regression were used to analyze the factors related to drug resistance, and a molecular network was constructed using 1.5%optimal gene distance. The drug resistance mutation sites were analyzed through the online tool HIV drug resistance database of Stanford University in the United States.

Results

Five gene subtypes were identified in 1 281 sequences, with the dominant subtype being CRF07_BC (92.58%). The HIV-1 resistance rate was 55.27%, while the resistance rates to Nucleoside reverse transcriptase inhibitors (NRTIs), Non-nucleoside reverse transcriptase inhibitors (NNRTIs), and Protease inhibitors (PIs) were 25.53%, 48.40%, and 7.57%. The main resistance sites were K103 (29.98%), M184 (22.79%), and Q58 (5.31%). Multivariable logistic regression indicated lower risk of drug resistance among females (OR=0.686, 95% CI=0.538-0.873), those aged 25-49 years (OR=0.444, 95% CI=0.245-0.804), patients on AZT+3TC+NVP/EFV (OR=0.506, 95% CI=0.375-0.683), and those with baseline CD4+ T-cell counts of 200-349 (cells/μL) (OR=0.547, 95% CI=0.400-0.750). By constructing a molecular network, a total of 62 transmission clusters were identified, with 402 patients entering the network, resulting in a network entry rate of 31.38%. A total of 173 patients developed drug resistance, with a resistance rate of 43.03%. Male patients had a higher network entry rate than female patients,and genetic subtypes CRF07_BC, CRF01_AE, and CRF55_01B all appeared in clusters.

Conclusion

The drug resistance rate of HIV/AIDS treatment failure patients in Urumqi is relatively high, and drug-resistant strains appear in clusters in the molecular network. It is necessary to strengthen drug resistance monitoring and reduce the clustered transmission of drug-resistant strains.

, authors=Ying-ying CUI1, Xuan GAO2, Yong-di HUANG2, Xiang LI1, Yi-hong ZHEN1, Man ZHANG1, -Jing LI1, Nuerla ADILA1, Xue BAI1, authorsList=Ying-ying CUI, Xuan GAO, Yong-di HUANG, Xiang LI, Yi-hong ZHEN, Man ZHANG, -Jing LI, Nuerla ADILA, Xue BAI, authorCompany=null, correspAuthors=Xue BAI, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1323941346154786979, articleId=1323941343294271641, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=乌鲁木齐市HIV/AIDS治疗失败患者耐药及分子网络特征分析, columnId=1228016573844226129, journalTitle=现代预防医学, columnName=疾病预防控制, runingTitle=null, highlight=null, articleAbstract=
目的

分析乌鲁木齐市HIV/AIDS治疗失败患者耐药情况及分子网络特征，为艾滋病防控工作提供理论依据。

方法

以2018—2023年在乌鲁木齐市艾滋病抗病毒治疗定点医疗机构接受治疗且病毒载量（VL）≥1 000拷贝/ml的1 281例治疗失败患者为研究对象，通过巢式PCR扩增HIV-1的pol区基因，采用Neighbor-joining方法构建系统进化树，利用χ2检验和logistic回归分析耐药相关影响因素，最适基因距离1.5%构建分子网络，通过美国斯坦福大学的在线工具HIV耐药数据库进行耐药突变位点的分析。

结果

1 281条序列中共发现5种基因亚型，优势亚型为CRF07_BC（92.58%）。HIV-1耐药率为55.27%，核苷类反转录酶抑制剂、非核苷类反转录酶抑制剂和蛋白酶抑制剂耐药率分别为25.53%、48.40%、7.57%，主要耐药位点分别为K103（29.98%）、M184（22.79%）、Q58（5.31%）。Logistic因素分析结果表明：女性（OR=0.686，95% CI：0.538～0.873）、25～49岁（OR=0.444，95% CI：0.245～0.804）、治疗方案齐多夫定+拉米夫定+奈韦拉平/依非韦伦（OR=0.506，95% CI：0.375～0.683）、初始CD4+T淋巴细胞数200～349（个/μl）（OR=0.547，95% CI：0.400～0.750）发生耐药的风险较低。通过构建分子网络，共发现62个传播簇，402例患者进入分子网络，入网率为31.38%；173例出现耐药，耐药率为43.03%；男性入网率高于女性；基因亚型CRF07_BC、CRF01_AE、CRF55_01B均成簇出现。

结论

乌鲁木齐市HIV/AIDS治疗失败患者耐药率较高且耐药株在分子网络中成簇出现，应加强耐药监测，降低耐药株的成簇传播。

, authors=崔莹莹1, 高璇2, 黄永迪2, 李翔1, 甄怡鸿1, 张曼1, 李婧1, 阿地拉·努尔拉1, 白雪1, authorsList=崔莹莹, 高璇, 黄永迪, 李翔, 甄怡鸿, 张曼, 李婧, 阿地拉·努尔拉, 白雪, authorCompany=null, correspAuthors=白雪, authorNote=

崔莹莹（1991—），女，硕士，助理研究员，研究方向：艾滋病预防与控制

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白雪，E-mail：
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崔莹莹（1991—），女，硕士，助理研究员，研究方向：艾滋病预防与控制

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(In Chinese), articleTitle=The first viral load suppression and its influencing factors for HIV/AIDS on ART in Shandong province, refAbstract=null), Reference(id=1323941359543005467, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, doi=null, pmid=null, pmcid=null, year=2024, volume=30, issue=5, pageStart=338, pageEnd=342, url=null, language=null, rfNumber=[24], rfOrder=43, authorNames=黄云, 傅连臣, journalName=预防医学论坛, refType=null, unstructuredReference=黄云，傅连臣. 2003-2020年山东省泰安市HIV-1患者抗病毒治疗耐药情况及影响因素分析 [J]. 预防医学论坛, 2024, 30 (5): 338-342., articleTitle=2003-2020年山东省泰安市HIV-1患者抗病毒治疗耐药情况及影响因素分析, refAbstract=null), Reference(id=1323941359610114333, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, doi=null, pmid=null, pmcid=null, year=2024, volume=30, issue=5, pageStart=338, pageEnd=342, url=null, language=null, rfNumber=[24], rfOrder=44, authorNames=Huang Y, Fu LC, journalName=Preventive Medicine Tribune, refType=null, unstructuredReference=Huang Y, Fu LC. 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Analysis of genotype drug resistance in HIV/AIDS patients who failed antiviral therapy [J]. Electronic Journal of Emerging Infectious Diseases, 2022, 7 (3): 37-40. 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Analysis on HIV subtypes, molecular clusters and drug resistance among newly reported infections in Heilongjiang Province in 2018 [J]. Chinese Journal of AIDS & STD, 2021, 27 (7): 680-684. (In Chinese), articleTitle=Analysis on HIV subtypes, molecular clusters and drug resistance among newly reported infections in Heilongjiang Province in 2018, refAbstract=null)], funds=[Fund(id=1323941354258182382, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, awardId=XJYS1706-2024006, language=CN, fundingSource=新疆艾滋病防控研究重点实验室开放课题项目(XJYS1706-2024006), fundOrder=null, country=null), Fund(id=1323941354371428591, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, awardId=202423, language=CN, fundingSource=乌鲁木齐市卫生健康委员会科技计划项目(202423), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1323941346398056612, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, xref=1., ext=[AuthorCompanyExt(id=1323941346406445221, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, companyId=1323941346398056612, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Urumqi Center for Disease Control and Prevention (Urumqi Health Supervision Institute), Urumqi, Xinjiang 830026, China), AuthorCompanyExt(id=1323941346419028134, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, companyId=1323941346398056612, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.乌鲁木齐市疾病预防控制中心（乌鲁木齐市卫生监督所），新疆　乌鲁木齐　830026)]), AuthorCompany(id=1323941346498719911, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, xref=2., ext=[AuthorCompanyExt(id=1323941346507108520, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, companyId=1323941346498719911, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.新疆维吾尔自治区疾病预防控制中心)])], figs=[ArticleFig(id=1323941351435415778, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=EN, label=Figure 1, caption=Distribution of HIV-1 genetic subtypes in patients with treatment failure in Urumqi City, figureFileSmall=1IBoB6J3Vr67oufN0uuCbA==, figureFileBig=daSa4KPP48VYviexc6q/5g==, tableContent=null), ArticleFig(id=1323941351536079075, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=CN, label=图1, caption=乌鲁木齐市治疗失败患者HIV-1基因亚型分布, figureFileSmall=1IBoB6J3Vr67oufN0uuCbA==, figureFileBig=daSa4KPP48VYviexc6q/5g==, tableContent=null), ArticleFig(id=1323941351729017060, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=EN, label=Figure 2, caption=Resistance level of antiviral drugs in patients with treatment failure, figureFileSmall=2oi17Z48JrkMdNMVc4qUgQ==, figureFileBig=AAmft1W6NUXXd9q0zoerWA==, tableContent=null), ArticleFig(id=1323941351800320229, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=CN, label=图2, caption=治疗失败患者对抗病毒药物的耐药程度, figureFileSmall=2oi17Z48JrkMdNMVc4qUgQ==, figureFileBig=AAmft1W6NUXXd9q0zoerWA==, tableContent=null), ArticleFig(id=1323941351875817702, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=EN, label=Figure 3, caption=Distribution of drug-resistant mutation sites in patients with treatment failure, figureFileSmall=rqL+PWPWnxLjUB7SZbz/fQ==, figureFileBig=Y1FU0VdUY+W1OLO3BpDTyQ==, tableContent=null), ArticleFig(id=1323941351938732263, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=CN, label=图3, caption=治疗失败患者耐药突变位点分布, figureFileSmall=rqL+PWPWnxLjUB7SZbz/fQ==, figureFileBig=Y1FU0VdUY+W1OLO3BpDTyQ==, tableContent=null), ArticleFig(id=1323941353725505768, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=EN, label=Figure 4, caption=Molecular network diagram of patients with treatment failure, figureFileSmall=TCJrr2M6oZvFpYaXm1Jjcw==, figureFileBig=waRTV0yCujBx61XTyI6VYA==, tableContent=null), ArticleFig(id=1323941353821974761, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=CN, label=图4, caption=治疗失败患者分子网络图, figureFileSmall=TCJrr2M6oZvFpYaXm1Jjcw==, figureFileBig=waRTV0yCujBx61XTyI6VYA==, tableContent=null), ArticleFig(id=1323941353880695018, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=EN, label=Table 1, caption=

Univariate analysis of drug resistance in patients with treatment failure

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总例数（构成比/%）耐药例数（耐药率，%）χ2值P值
性别14.3300.000
男性793(61.90)471(59.39)
女性488(38.10)237(48.57)
年龄（岁）9.0880.011
<2599(7.73)67(67.68)
25～491 033(80.64)569(55.08)
≥50149(11.63)72(48.32)
文化程度5.1720.270
文盲56(4.37)28(50.00)
小学219(17.10)127(57.99)
初中458(35.75)242(52.84)
高中或中专307(23.97)183(59.61)
大专及以上241(18.81)128(53.11)
婚姻状况0.029*
未婚348(27.17)210(60.34)
已婚有配偶599(46.76)333(55.59)
离异或丧偶329(25.68)162(49.24)
不详5(0.39)3(60.00)
感染途径5.3180.150
静脉吸毒369(28.81)195(52.85)
同性传播85(6.64)51(60.00)
异性传播758(59.17)416(54.88)
其他69(5.39)46(66.67)
初始治疗方案24.4480.000
TDF+3TC+NVP/EFV502(39.19)296(58.96)
AZT+3TC+NVP/EFV484(37.78)286(59.09)
其他295(23.03)126(42.71)
初始CD4+T淋巴细胞数（个/μl）12.6920.002
<200239(18.66)155(64.85)
200～349354(27.63)198(55.93)
≥350688(53.71)355(51.60)
基因亚型0.000*
CRF07_BC1 186(92.58)639(53.88)
CRF01_AE46(3.59)29(63.04)
CRF55_01B33(2.58)30(90.91)
B13(1.01)9(69.23)
CRF08_BC3(0.23)1(33.33)
治疗时长（年）0.5630.755
<1130（10.15）68（52.31）
1～3343（26.77）189（55.10）
≥3808（63.08）451（55.82）
), ArticleFig(id=1323941353960386795, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=CN, label=表1, caption=

治疗失败患者耐药单因素分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总例数（构成比/%）耐药例数（耐药率，%）χ2值P值
性别14.3300.000
男性793(61.90)471(59.39)
女性488(38.10)237(48.57)
年龄（岁）9.0880.011
<2599(7.73)67(67.68)
25～491 033(80.64)569(55.08)
≥50149(11.63)72(48.32)
文化程度5.1720.270
文盲56(4.37)28(50.00)
小学219(17.10)127(57.99)
初中458(35.75)242(52.84)
高中或中专307(23.97)183(59.61)
大专及以上241(18.81)128(53.11)
婚姻状况0.029*
未婚348(27.17)210(60.34)
已婚有配偶599(46.76)333(55.59)
离异或丧偶329(25.68)162(49.24)
不详5(0.39)3(60.00)
感染途径5.3180.150
静脉吸毒369(28.81)195(52.85)
同性传播85(6.64)51(60.00)
异性传播758(59.17)416(54.88)
其他69(5.39)46(66.67)
初始治疗方案24.4480.000
TDF+3TC+NVP/EFV502(39.19)296(58.96)
AZT+3TC+NVP/EFV484(37.78)286(59.09)
其他295(23.03)126(42.71)
初始CD4+T淋巴细胞数（个/μl）12.6920.002
<200239(18.66)155(64.85)
200～349354(27.63)198(55.93)
≥350688(53.71)355(51.60)
基因亚型0.000*
CRF07_BC1 186(92.58)639(53.88)
CRF01_AE46(3.59)29(63.04)
CRF55_01B33(2.58)30(90.91)
B13(1.01)9(69.23)
CRF08_BC3(0.23)1(33.33)
治疗时长（年）0.5630.755
<1130（10.15）68（52.31）
1～3343（26.77）189（55.10）
≥3808（63.08）451（55.82）
), ArticleFig(id=1323941354040078572, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=EN, label=Table 2, caption=

Multivariable logistic regression analysis in patients with treatment failure

, figureFileSmall=null, figureFileBig=null, tableContent=
变量参照组β标准误Wald值P值OR值（95% CI）
性别
女性男性-0.3780.1239.3710.0020.686（0.538～0.873）
年龄（岁）
25～49<25-0.8130.3037.1740.0070.444（0.245～0.804）
≥50-0.2880.1852.4350.1190.750（0.522～1.077）
婚姻状况
已婚有配偶未婚-0.0850.9280.0080.9270.918（0.149～5.662）
离异或丧偶-0.1210.9250.0170.8960.886（0.145～5.431）
不详-0.0870.9290.0090.9251.091（0.177～6.732）
初始治疗方案
AZT+3TC+NVP/EFVTDF+3TC+NVP/EFV-0.6810.15319.8110.0000.506（0.375～0.683）
其他-0.6800.15419.5080.0000.507（0.374～0.685）
初始CD4+T淋巴细胞数（个/μl）
200～349<200-0.6020.16114.0620.0000.547（0.400～0.750）
≥350-0.1490.1371.1860.2760.862（0.659～1.126）
基因亚型
CRF01_AECRF07_BC-0.6891.2710.2940.5880.502（0.042～6.067）
CRF55_01B-0.8231.3080.3950.5300.439（0.034～5.708）
B-2.6471.4103.5240.0600.071（0.004～1.124）
CRF08_BC-1.1931.4110.7150.3980.303（0.019～4.815）
), ArticleFig(id=1323941354115576045, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941343294271641, language=CN, label=表2, caption=

治疗失败患者logistic回归多因素分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变量参照组β标准误Wald值P值OR值（95% CI）
性别
女性男性-0.3780.1239.3710.0020.686（0.538～0.873）
年龄（岁）
25～49<25-0.8130.3037.1740.0070.444（0.245～0.804）
≥50-0.2880.1852.4350.1190.750（0.522～1.077）
婚姻状况
已婚有配偶未婚-0.0850.9280.0080.9270.918（0.149～5.662）
离异或丧偶-0.1210.9250.0170.8960.886（0.145～5.431）
不详-0.0870.9290.0090.9251.091（0.177～6.732）
初始治疗方案
AZT+3TC+NVP/EFVTDF+3TC+NVP/EFV-0.6810.15319.8110.0000.506（0.375～0.683）
其他-0.6800.15419.5080.0000.507（0.374～0.685）
初始CD4+T淋巴细胞数（个/μl）
200～349<200-0.6020.16114.0620.0000.547（0.400～0.750）
≥350-0.1490.1371.1860.2760.862（0.659～1.126）
基因亚型
CRF01_AECRF07_BC-0.6891.2710.2940.5880.502（0.042～6.067）
CRF55_01B-0.8231.3080.3950.5300.439（0.034～5.708）
B-2.6471.4103.5240.0600.071（0.004～1.124）
CRF08_BC-1.1931.4110.7150.3980.303（0.019～4.815）
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乌鲁木齐市HIV/AIDS治疗失败患者耐药及分子网络特征分析
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崔莹莹 1 , 高璇 2 , 黄永迪 2 , 李翔 1 , 甄怡鸿 1 , 张曼 1 , 李婧 1 , 阿地拉·努尔拉 1 , 白雪 1
现代预防医学 | 疾病预防控制 2025,52(23): 4396-4402
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现代预防医学 |疾病预防控制 2025 , 52 (23) : 4396 -4402
乌鲁木齐市HIV/AIDS治疗失败患者耐药及分子网络特征分析
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崔莹莹1, 高璇2, 黄永迪2, 李翔1, 甄怡鸿1, 张曼1, 李婧1, 阿地拉·努尔拉1, 白雪1
作者信息
  • 1.乌鲁木齐市疾病预防控制中心（乌鲁木齐市卫生监督所），新疆　乌鲁木齐　830026
  • 2.新疆维吾尔自治区疾病预防控制中心
通讯作者:
白雪，E-mail：
作者简介:

崔莹莹（1991—），女，硕士，助理研究员，研究方向：艾滋病预防与控制

Drug resistance and molecular network characteristics among HIV/AIDS patients with treatment failure in Urumqi City
Ying-ying CUI1, Xuan GAO2, Yong-di HUANG2, Xiang LI1, Yi-hong ZHEN1, Man ZHANG1, -Jing LI1, Nuerla ADILA1, Xue BAI1
Affiliations
  • Urumqi Center for Disease Control and Prevention (Urumqi Health Supervision Institute), Urumqi, Xinjiang 830026, China
出版时间: 2025-12-10 doi: 10.20043/j.cnki.MPM.202502190
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摘要
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目的

分析乌鲁木齐市HIV/AIDS治疗失败患者耐药情况及分子网络特征，为艾滋病防控工作提供理论依据。

方法

以2018—2023年在乌鲁木齐市艾滋病抗病毒治疗定点医疗机构接受治疗且病毒载量（VL）≥1 000拷贝/ml的1 281例治疗失败患者为研究对象，通过巢式PCR扩增HIV-1的pol区基因，采用Neighbor-joining方法构建系统进化树，利用χ2检验和logistic回归分析耐药相关影响因素，最适基因距离1.5%构建分子网络，通过美国斯坦福大学的在线工具HIV耐药数据库进行耐药突变位点的分析。

结果

1 281条序列中共发现5种基因亚型，优势亚型为CRF07_BC（92.58%）。HIV-1耐药率为55.27%，核苷类反转录酶抑制剂、非核苷类反转录酶抑制剂和蛋白酶抑制剂耐药率分别为25.53%、48.40%、7.57%，主要耐药位点分别为K103（29.98%）、M184（22.79%）、Q58（5.31%）。Logistic因素分析结果表明：女性（OR=0.686，95% CI：0.538～0.873）、25～49岁（OR=0.444，95% CI：0.245～0.804）、治疗方案齐多夫定+拉米夫定+奈韦拉平/依非韦伦（OR=0.506，95% CI：0.375～0.683）、初始CD4+T淋巴细胞数200～349（个/μl）（OR=0.547，95% CI：0.400～0.750）发生耐药的风险较低。通过构建分子网络，共发现62个传播簇，402例患者进入分子网络，入网率为31.38%；173例出现耐药，耐药率为43.03%；男性入网率高于女性；基因亚型CRF07_BC、CRF01_AE、CRF55_01B均成簇出现。

结论

乌鲁木齐市HIV/AIDS治疗失败患者耐药率较高且耐药株在分子网络中成簇出现，应加强耐药监测，降低耐药株的成簇传播。

HIV-1  /  抗病毒治疗  /  耐药  /  影响因素  /  分子网络
Objective

To analyze the drug resistance and molecular network characteristics of HIV/AIDS treatment failure patients in Urumqi City, and provide a theoretical basis for AIDS prevention and control.

Methods

A total of 1 281 patients who received antiviral treatment in AIDS antiviral designated medical institutions in Urumqi City from 2018 to 2023 and had a viral load (VL) ≥1 000 copies/mL were classified as treatment failure patients and included. The pol region gene of HIV-1 was amplified by nested PCR, and a phylogenetic tree was constructed using the neighbor-joining method. χ2 text and logistic regression were used to analyze the factors related to drug resistance, and a molecular network was constructed using 1.5%optimal gene distance. The drug resistance mutation sites were analyzed through the online tool HIV drug resistance database of Stanford University in the United States.

Results

Five gene subtypes were identified in 1 281 sequences, with the dominant subtype being CRF07_BC (92.58%). The HIV-1 resistance rate was 55.27%, while the resistance rates to Nucleoside reverse transcriptase inhibitors (NRTIs), Non-nucleoside reverse transcriptase inhibitors (NNRTIs), and Protease inhibitors (PIs) were 25.53%, 48.40%, and 7.57%. The main resistance sites were K103 (29.98%), M184 (22.79%), and Q58 (5.31%). Multivariable logistic regression indicated lower risk of drug resistance among females (OR=0.686, 95% CI=0.538-0.873), those aged 25-49 years (OR=0.444, 95% CI=0.245-0.804), patients on AZT+3TC+NVP/EFV (OR=0.506, 95% CI=0.375-0.683), and those with baseline CD4+ T-cell counts of 200-349 (cells/μL) (OR=0.547, 95% CI=0.400-0.750). By constructing a molecular network, a total of 62 transmission clusters were identified, with 402 patients entering the network, resulting in a network entry rate of 31.38%. A total of 173 patients developed drug resistance, with a resistance rate of 43.03%. Male patients had a higher network entry rate than female patients,and genetic subtypes CRF07_BC, CRF01_AE, and CRF55_01B all appeared in clusters.

Conclusion

The drug resistance rate of HIV/AIDS treatment failure patients in Urumqi is relatively high, and drug-resistant strains appear in clusters in the molecular network. It is necessary to strengthen drug resistance monitoring and reduce the clustered transmission of drug-resistant strains.

HIV-1  /  Antiviral therapy  /  Drug resistance  /  Influencing factors  /  Molecular network
崔莹莹, 高璇, 黄永迪, 李翔, 甄怡鸿, 张曼, 李婧, 阿地拉·努尔拉, 白雪. 乌鲁木齐市HIV/AIDS治疗失败患者耐药及分子网络特征分析. 现代预防医学, 2025 , 52 (23) : 4396 -4402 . DOI: 10.20043/j.cnki.MPM.202502190
Ying-ying CUI, Xuan GAO, Yong-di HUANG, Xiang LI, Yi-hong ZHEN, Man ZHANG, -Jing LI, Nuerla ADILA, Xue BAI. Drug resistance and molecular network characteristics among HIV/AIDS patients with treatment failure in Urumqi City[J]. Modern Preventive Medicine, 2025 , 52 (23) : 4396 -4402 . DOI: 10.20043/j.cnki.MPM.202502190
正文
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随着艾滋病抗病毒治疗（antiretroviral therapy，ART）的普及，耐药性问题逐渐成为临床和公共健康关注的焦点。耐药性的出现不仅会降低ART的效果，增加患者治疗难度和成本，也使得艾滋病防控工作更加复杂和艰难[1-2]。目前，基于两条序列间基因距离所构建的分子传播网络分析技术也广泛运用于国内外相关研究，使我们能够更加全面地重构宏观层面的感染者社会网络，能够更加直观且高效地揭示艾滋病的传播特点[3]。我国近年各地区流行亚型和获得性耐药水平存在差异，耐药率随着ART时间的延长呈上升趋势，总体的获得性耐药率为44.7%，非核苷类反转录酶抑制(non-nudeoside transciptase reverse inhibitor,NNRTI)耐药比核苷类反转录酶抑制剂(nucleoside reverse transcriptase inhilbirors,NRTIs)耐药更普遍。欧美等高收入国家呈稳定或下降趋势[1,4]。乌鲁木齐市作为新疆维吾尔自治区首府城市，是最早开始艾滋病ART的地区之一。同时作为新疆政治、经济、文化和交通枢纽，人口流动性大，加速了耐药株的传播，使得本地区耐药问题日益突显，进而造成患者治疗整体效果下降与病毒学失败率升高[5]。2016年乌鲁木齐市获得性耐药率达55.81%[6]，然而近年来对获得性耐药数据更新及系统性分析却未有报道，本研究将通过对乌鲁木齐市ART失败患者进行耐药检测，并对耐药基因亚型、突变位点、影响因素、分子网络特征等进行分析，为后续研究及完善艾滋病ART策略提供依据，为预防耐药毒株传播和提高ART效果提供参考。
1　对象与方法
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1.1　对象
选择2018—2023年在乌鲁木齐市艾滋病抗病毒定点医疗机构接受ART≥6个月且病毒载量（VL）≥1 000拷贝/ml的治疗失败患者[7-8]。排除标准：（1）HIV-1测序失败样本；（2）相同HIV/AIDS患者的重复序列；（3）人口学信息缺失或错误样本。本研究通过乌鲁木齐市疾病预防控制中心（乌鲁木齐市卫生监督所）伦理委员会审查批准（2024-C112）。
1.2　方法
1.2.1　信息收集
从中国疾病预防控制信息系统下载并整理2018—2023年在乌鲁木齐市艾滋病ART定点医疗机构接受治疗的HIV感染者/AIDS患者的人口学信息、ART及相关检测数据。
1.2.2　病毒载量检测
试剂使用美国罗氏诊断公司核酸定量试剂盒；仪器使用罗氏配套的CobasTaqMan全自动病毒载量检测工作站，最低检出限为20拷贝/ml。实验操作严格按照说明书进行。对病毒载量（VL）≥1 000拷贝/ml全血标本以3 000 r/min离心15 min，血浆分装后保存于-80℃冰箱以备耐药检测。
1.2.3　耐药检测
对HIV-1 pol区采用巢氏聚合酶链式反应(polymerase chain reaction，PCR)进行基因扩增。扩增产物由北京德宏昌远生物科技有限公司进行产物纯化及序列测定。测定结果上传至美国斯坦福大学在线工具HIV耐药数据库（https://hivdb.stanford.edu/）进行耐药状态、耐药种类及耐药程度分析。耐药程度分为五个级别：敏感（S）、潜在耐药（P）、低度耐药（L）、中度耐药（I）、高度耐药（H）。对任一药物预测耐药级别为低度及以上耐药则判定为耐药。通过BLAST及采用MEGA11.0软件中的邻接法进行系统进化树的构建及基因亚型的判定。对七种NRTIs五种NNRTIs和八种蛋白酶抑制剂(protease inhibitors,PIs）进行耐药情况分析。七种NRTIs：恩曲他滨（FTC）、阿巴卡韦（ABC）、齐多夫定（AZT）、司他夫定（D4T）、去羟肌苷（DDI）、替诺福韦（TDF）、拉米夫定（3TC）；五种NNRTIs：依非韦仑（EFV）、多拉韦林（DOR）、依曲伟林（ETR）、利匹韦林（RPV）、奈韦拉平（NVP）；八种PIs：茚地那韦/利托那韦（IDV/r）、阿扎那韦/利托那韦（ATV/r）、奈非那韦（NFV）、达芦那韦/利托那韦（DRV/r）、福沙那韦/利托那韦（FPV/r）、替拉那韦/利托那韦（TPV/r）、洛匹那韦/利托那韦（LPV/r）、沙奎那韦/利托那韦（SQV/r）。
1.2.4　分子网络构建
通过HyPhy 2.2.1软件中的模型TN93计算序列间的基因距离，选择成簇最多的1.5%基因距离为阈值，使用Cytoscape 3.10.2软件实现网络的构建及可视化。
1.2.5　统计分析
采用Excel 2016和SPSS 23.0软件进行资料的整理和统计分析，使用χ2检验和logistic回归模型对耐药影响因素进行分析，检验水准α=0.05。
2　结果
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2.1　一般人口学信息
在纳入研究的1 281例治疗失败患者中，以男性（793例，61.90%）、25～49岁（1 033例，80.64%）、初中（458例，35.75%）、已婚有配偶（599例，46.76%）、异性传播（758例，59.17%）、初始治疗方案TDF+3TC+NVP/EFV（502例，39.19%）、初始CD4+T淋巴细胞数≥350（个/μl）（688例，53.71%）为主，按照HIV-1pol区序列初步分型，基因亚型以CRF07_BC（1 186例，92.58%）为主。见表1、图1。
2.2　耐药及突变位点分析
1 281例中有708例对一种或多种药物产生耐药，耐药率为55.27%（708/1 281）。其中，NRTIs的耐药率为25.53%（327/1 281），NNRTIs的耐药率为48.40%（620/1 281），PIs的耐药率为7.57%（97/1 281）。对NRTIs和NNRTIs类药物双重耐药率较高，为21.78%（279/1 281），对NRTIs和PIs双重耐药率为0.94%（12/1 281），对NNRTIs和PIs双重耐药率为1.48%（19/1 281），对三类药物同时耐药率为2.03（26/1 281）。NNRTIs中耐药发生率较高的是NVP（44.42%），其次是EFV（44.18%）且均以高度耐药为主，耐药位点出现频率较高的是K103（29.98%），其次是V106（9.60%）；NRTIs中耐药发生率较高的是ABC（24.36%），其次是3TC、FTC的耐药率均为24.04%，且分别以低度耐药和高度耐药为主，耐药位点出现频率较高的是M184（22.79%），其次是K70（5.70%）；PIs中耐药发生率较高的是TPV/r（6.17%），且以低度耐药为主，耐药位点主要是Q58（5.31%），其次是V82（1.33%）。见图2、3。
2.3　耐药影响因素分析
单因素分析结果显示，文化程度、感染途径、治疗时长对患者耐药率的差异无统计学意义。将单因素分析中P<0.05的变量进行多因素logistic回归分析结果显示，女性（OR=0.686，95% CI：0.538～0.873）、25～49岁（OR=0.444， 95% CI：0.245～0.804）、治疗方案AZT+3TC+NVP/EFV （OR=0.506，95% CI：0.375～0.683）、初始CD4+T淋巴细胞数200～349（个/μl）（OR=0.547，95% CI：0.400～0.750）发生耐药的风险较低。见表1、2。
2.4　分子网络分析
最适基因距离1.5%阈值下，共发现62个传播簇，最大簇包含241个节点，有402例HIV/AIDS患者进入分子网络，入网率为31.38%（402/1 281），其中男性入网率为62.94%（253/402），女性入网率为37.06%（149/402）。402例成簇的HIV/AIDS患者中173例出现耐药，耐药率为43.03%。共发现13个≥3个节点的簇，其中仅由男性组成的有4个簇，其中1个簇有节点25个；CRF01_AE、CRF55_01B传播簇各1个，且均为男性，其余均为CRF07_BC的传播簇；共有10个簇（76.92%）检测到耐药序列且均包含耐药位点K103，4个簇（40%）包含耐药位点M184。见图4。
3　讨论
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本研究结果显示，2018—2023年乌鲁木齐市1 281例艾滋病ART 失败患者以25～49岁（80.64%）、男性（61.90%）、初中（35.75%）、异性传播（59.17%）、初治方案TDF+3TC+NVP/EFV（39.19%）、初始CD4+T淋巴细胞计数≥350（个/μl）（53.71%）为主，HIV-1基因型主要为CRF07_BC亚型（92.58%），与新疆地区报道结果相一致，但与乌鲁木齐市2014年（50.00%）相比较，CRF07_BC亚型比例大幅上升[9-11]，说明随着治疗的延长，耐药毒株不断传播。
2018—2023年乌鲁木齐市治疗失败患者耐药率为55.27%，较低于2020—2021年新疆阿克苏地区同类人群耐药率（58.5%）[10]，较高于吐鲁番地区（42.86%）、伊犁州（44.15%）等地的耐药率[6]。与宁夏（39.88%）、成都（48.1%）、吉林省（58.8% ）、山西省（59.29%）等同类人群耐药率相比[12-15]，乌鲁木齐市ART 失败人群耐药处于较高水平，这可能与乌鲁木齐市作为南北疆枢纽城市，人口流动性大，导致的中断治疗患者较多且与早期吸毒患者较多有关，提示应加强耐药监测，降低耐药发生率。本研究结果显示NNRTIs的耐药率高于NRTIs、PIs，与大多数研究结果相符[16-17]，这与乌鲁木齐市早期多使用一线治疗方案且 NNRTIs有较低的耐药屏障更容易发生耐药有关。NNRTIs和NRTIs耐药突变位点以K103和M184为主，NNRTIs药物中NVP（44.42%）和 EFV（44.18%）耐药率较高，NRTIs药物中以ABC（24.36%）耐药较为常见，与新疆伊犁、阿克苏地区及国内外同类研究结果一致[5,10,15,18-21]。提示应根据耐药情况及时调整治疗方案。
耐药影响因素结果表明，男性、年龄<25岁、CD4+T淋巴细胞计数<200个/μl是患者耐药的风险因素。ART 失败患者中以男性为主且小于25岁年轻患者对治疗、社会心理认知及治疗时无明显症状等因素导致的服药依从性较差，加剧了耐药发生风险，与既往研究一致[22]。CD4+T淋巴细胞值越低，发生耐药的可能性越大，与多数研究结果一致[23-24]。因此，要在初始 CD4+T 淋巴细胞计数水平较高时及时开展治疗[25]，尽早对低年龄组患者进行服药依从性教育并对不同亚型的耐药情况进行监测，以减少HIV的感染及控制耐药株的传播。
构建分子网络结果显示，入网率为31.38%，相对于未入网个体，入网的个体相互间可能存在潜在的传播关系，其传播风险可能更高[3]，本研究中近三分之一感染者处于活跃分子传播簇中，应结合流调及溯源调查，优先对此部分群体进行性伴追踪及干预，以降低耐药株传播。入网序列中 43.03% 为耐药毒株，76.92% 的分子簇包含耐药位点，提示可能存在耐药毒株传播。进入网络的CRF07 _BC、CRF01_AE、CRF55_01B和B这4种亚型间不存在相互连接，彼此各自成簇，表明乌鲁木齐市这4种亚型已出现成簇传播且亚型之间的基因距离已大于最适的基因距离，应加强耐药的长期监测并不断完善分子网络，降低耐药株的成簇传播，避免耐药株间的交叉传播。CRF07_BC 的分子传播簇在网络中连接率高于其它三种亚型，其传播关系更紧密，这更证明了CRF07_BC在中国具有广泛的传播趋势[26-27]。研究发现≥3个节点的簇13个，其中仅由男性组成的簇有4个，且其中1个簇有25个节点，分子簇中均为男性，CRF07_BC亚型且大多感染途径为同性传播，因此，可能存在潜在未公开或报告的男男同性性行为人群[10,28]，因此，要加大对该高危人群的干预与关怀力度[29]。
综上，本次对乌鲁木齐市2018—2023年治疗失败患者进行了较为系统的耐药情况和分子网络分析，揭示了一定的传播特征，识别出若干传播簇。乌鲁木齐市耐药发生率较高且耐药株在网络中成簇出现，以NNRTIs类药物耐药为主，存在NNRTIs与NRTIs、PIs类药物的多重耐药。本研究也存在一定局限性，未开展整合酶抑制剂类药物以及gag和env等区域的分析且未纳入服药依从性等影响因素的分析，这些缺失可能在统计过程中引入一定的偏倚，后续将扩大监测并结合HIV感染者服药依从性开展治疗效果评估，做好溯源随访工作，以防止耐药病毒株进一步传播，降低乌鲁木齐的耐药发生率。
基金
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  • 新疆艾滋病防控研究重点实验室开放课题项目(XJYS1706-2024006)
  • 乌鲁木齐市卫生健康委员会科技计划项目(202423)
文献
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2025年第52卷第23期
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doi: 10.20043/j.cnki.MPM.202502190
  • 接收时间：2025-02-13
  • 首发时间：2026-11-02
  • 出版时间：2025-12-10
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  • 收稿日期：2025-02-13
基金
新疆艾滋病防控研究重点实验室开放课题项目(XJYS1706-2024006)
乌鲁木齐市卫生健康委员会科技计划项目(202423)
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    1.乌鲁木齐市疾病预防控制中心（乌鲁木齐市卫生监督所），新疆　乌鲁木齐　830026
    2.新疆维吾尔自治区疾病预防控制中心

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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
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
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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