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Article(id=1240413926060511880, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240413921266429979, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202503276, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1741968000000, receivedDateStr=2025-03-15, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773667325748, onlineDateStr=2026-03-16, pubDate=1754755200000, pubDateStr=2025-08-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773667325748, onlineIssueDateStr=2026-03-16, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773667325748, creator=13701087609, updateTime=1773667325748, updator=13701087609, issue=Issue{id=1240413921266429979, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='15', pageStart='2689', pageEnd='2880', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1773667324606, creator=13701087609, updateTime=1773667356299, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1240414054267802325, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240413921266429979, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1240414054267802326, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240413921266429979, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=2860, endPage=2865, ext={EN=ArticleExt(id=1240413926400250507, articleId=1240413926060511880, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Pre-treatment and acquired drug resistance characteristics among HIV-1-infected individuals in Hebei Province, China, columnId=1228016573156360233, journalTitle=Modern Preventive Medicine, columnName=Disease Control and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the epidemiology and influencing factors of pre-treatment drug resistance (PDR) and acquired drug resistance(ADR) in Hebei Province.

Methods

Plasma samples were collected from HIV-1-infected individuals who were ART-naive or experiencing ART failure in Hebei Province from January 2022 to December 2023 to determine drug resistance profiles. Multivariate logistic regression was used to analyze the influencing factors of drug resistance.

Results

The overall prevalence of PDR were 9.19%, showing a moderate prevalence trend. The overall prevalence of ADR was 46.71%,presenting a high level of drug resistance and the phenomenon of cross drug resistance. Multivariate logistic regression analysis showed that start ART more than one year after diagnosis (OR=3.007, 95% CI: 1.185-7.633) and being infected with subtypes other than CRF07_BC, subtype B, and URFs (OR=3.227, 95% CI: 1.043-9.991) were risk factors for PDR. Non-farmer occupation(OR=1.787, 95% CI: 1.129-2.830) and 3-5 years treatment duration(OR=2.440, 95% CI: 1.422-4.185) were risk factors for ADR, while CD4+T-cell counts between 200-500 cells/μl (OR=0.382, 95% CI: 0.236-0.618) and above 500 cells/μl(OR=0.158, 95% CI: 0.083-0.299), second-line regimens containing LPV/r or BIC (OR=0.229, 95% CI: 0.083-0.629; OR=0.064,95% CI: 0.008-0.534), and CRF07_BC(OR=0.398, 95% CI: 0.245-0.647) were protective factors for ADR.

Conclusion

Monitoring of local PDR and ADR should be strengthened to know about the situation of drug resistance as early as possible, and targeted interventions should be taken to reduce the spread of HIV-1 drug-resistant strains.

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目的

了解河北省治疗前耐药（pre-treatment drug resistance，PDR）和获得性耐药（acquired drug resistance，ADR）流行情况及耐药影响因素。

方法

分别抽取2022年1月—2023年12月河北省治疗前和治疗失败HIV-1感染者的血浆样本进行耐药特征的判定，多因素logistic回归进行耐药影响因素分析。

结果

河北省PDR总体流行率为9.19%，处于中度流行态势；河北省ADR总体流行率为46.71%，ADR耐药率高且多呈现高度耐药，多重耐药现象。Logistic回归分析显示：确诊后超过1年启动抗逆转录病毒治疗（antiretroviral therapy，ART）（OR=3.007，95%CI：1.185～7.633）以及感染非CRF07_BC、B、URFs外的其他亚型（OR=3.227，95%CI：1.043～9.991）是PDR的危险因素；非农民职业（OR=1.787，95%CI：1.129～2.830）、治疗时长在3～5年（OR=2.440，95%CI：1.422～4.185）是ADR的危险因素，CD4+T淋巴细胞计数水平在200～500个/μl之间以及在500个/μl以上（OR=0.382，95%CI：0.236～0.618；OR=0.158，95%CI：0.083～0.299）、包含LPV/r或BIC的二线治疗方案（OR=0.229，95%CI：0.083～0.629；OR=0.064，95%CI：0.008～0.534）、CRF07_BC（OR=0.398，95%CI：0.245～0.647）是ADR的保护因素。

结论

发现即治疗的大背景下，应加强对当地PDR和ADR水平的监测，尽早发现耐药的流行情况，针对性采取措施降低HIV-1耐药毒株的传播，实施高质量的精准干预治疗。

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路新利，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=VlrXhwJ7IE1PUv9vDRGzkA==, magXml=RwD5fN5+kbYM/uIAhE7BMg==, pdfUrl=null, pdf=fRfjLHiebYIl6+xLmHXJZA==, pdfFileSize=631556, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=r5VPrfLqhk3zUKggjvmZTg==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=Il5vrFaNWt8bvHZ82jnLMg==, mapNumber=null, authorCompany=null, fund=null, authors=

刘萌（1991—），女，硕士，主管技师，研究方向：艾滋病防控

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刘萌（1991—），女，硕士，主管技师，研究方向：艾滋病防控

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刘萌（1991—），女，硕士，主管技师，研究方向：艾滋病防控

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Analysis of HIV-1 genotype resistance test of HIV antiviral therapy failures, 2019-2020, in Shanxi province[J].Chinese Journal of Experimental and Clinical Virology, 2022, 36(2): 176-182.(In Chinese), articleTitle=Analysis of HIV-1 genotype resistance test of HIV antiviral therapy failures, 2019-2020, in Shanxi province, refAbstract=null), Reference(id=1240424353259647623, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, doi=null, pmid=null, pmcid=null, year=2009, volume=83, issue=4, pageStart=2038, pageEnd=2043, url=null, language=null, rfNumber=[14], rfOrder=20, authorNames=Paredes R, Sagar M, Marconi VC, journalName=Journal of Virology, refType=null, unstructuredReference=Paredes R, Sagar M, Marconi VC, et al. In vivo fitness cost of the M184V mutation in multidrug-resistant human immunodeficiency virus type 1 in the absence of lamivudine[J]. 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Effect of timing on initiation of antiviral therapy after diagnosis on viral suppression in HIV-infected patients[J].Chinese Journal of AIDS & STD, 2021, 27(11): 1218-1223.(In Chinese), articleTitle=Effect of timing on initiation of antiviral therapy after diagnosis on viral suppression in HIV-infected patients, refAbstract=null), Reference(id=1240424353670689445, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, doi=null, pmid=null, pmcid=null, year=2023, volume=329, issue=1, pageStart=63, pageEnd=84, url=null, language=null, rfNumber=[16], rfOrder=23, authorNames=Gandhi RT, Bedimo R, Hoy JF, journalName=JAMA: the Journal of the American Medical Association, refType=null, unstructuredReference=Gandhi RT, Bedimo R, Hoy JF, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2022 recommendations of the international antiviral Society-USA panel[J].JAMA: the Journal of the American Medical Association, 2023, 329(1): 63-84., articleTitle=Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2022 recommendations of the international antiviral Society-USA panel, refAbstract=null)], funds=[Fund(id=1240424349132452274, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, awardId=20220048, language=CN, fundingSource=2022年度河北省医学科学研究课题计划(20220048), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1240424342887133340, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, xref=null, ext=[AuthorCompanyExt(id=1240424342895521950, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, companyId=1240424342887133340, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of STD and AIDS Research, Hebei Provincial Center for Disease Control and Prevention, Hebei Key Laboratory of Pathogen and Epidemiology of Infectious Disease, Shijiazhuang, Hebei Province 050021, China), AuthorCompanyExt(id=1240424342903910560, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, companyId=1240424342887133340, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=河北省疾病预防控制中心性病艾滋病防治所，河北省传染病病原学鉴定分析与流行病学重点实验室，河北 石家庄 050021)])], figs=[ArticleFig(id=1240424347932881253, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, language=EN, label=Figure 1, caption=Resistance levels to antiretroviral drugs among ART naive and ART failure, figureFileSmall=xiTw0JrKdagx5/PE3BUcsw==, figureFileBig=43/bfQvKmenB1Bh9cOfuGA==, tableContent=null), ArticleFig(id=1240424348058710379, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, language=CN, label=图1, caption=治疗前及治疗失败感染者对抗病毒药物的耐药水平分析

注：ATV/r为阿扎那韦；DRV/r为达芦那韦；FPV/r为福沙那韦；IDV/r为茚地那韦；NFV为奈非那韦；SQV/r为沙奎那韦；TPV/r为替拉那韦；ABC为阿巴卡韦；D4T为司他夫定；DDI为去羟肌苷；DOR为多拉韦林；ETR为依曲韦林；NVP为奈韦拉平；RPV为利匹韦林；图A为治疗前；图B为治疗失败。

, figureFileSmall=xiTw0JrKdagx5/PE3BUcsw==, figureFileBig=43/bfQvKmenB1Bh9cOfuGA==, tableContent=null), ArticleFig(id=1240424348180345207, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, language=EN, label=Table 1, caption=

Demographic and subtype characteristics of ART naive and ART failure ［n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
变量治疗前治疗失败变量治疗前治疗失败
性别病毒载量（copies/ml）
男性416（91.03）446（91.77）>103～104—163（33.54）
女性41（8.97）40（8.23）>104～105—200（41.15）
民族>105—123（25.31）
汉族441（96.50）445（91.56）ART启动时间（年）
少数民族16（3.50）41（8.44）≤1423（92.56）—
年龄（岁）>134（7.44）—
18～29126（27.57）84（17.28）治疗时长（年）
30～49197（43.11）257（52.88）<3—279（57.41）
≥50134（29.32）145（29.84）3～5—105（21.60）
婚姻状况>5～10—91（18.72）
未婚175（38.29）177（36.42）>10—11（2.26）
已婚或有配偶232（50.77）261（53.70）治疗方案
离异或丧偶50（10.94）48（9.88）TDF+3TC+EFV—306（62.96）
职业AZT/3TC+EFV—30（6.17）
农民121（26.48）211（43.42）TDF+3TC+LPV/r—27（5.56）
学生27（5.91）14（2.88）BIC/FTC/TAF—16（3.29）
其他职业309（67.61）261（53.70）TDF+3TC+DTG—15（3.09）
感染途径其他—92（18.93）
同性性传播345（75.49）362（74.49）亚型
异性性传播109（23.85）111（22.84）CRF01_AE206（45.08）230（47.33）
其他3（0.66）13（2.67）CRF07_BC181（39.61）162（33.33）
CD4+T细胞计数（个/μl）B27（5.91）60（12.35）
<200108（23.63）194（39.92）URFs12（2.63）10（2.06）
200～500299（65.43）192（39.51）其他31（6.78）a24（4.94）b
>50050（10.94）100（20.58）合计457（100.00）486（100.00）
), ArticleFig(id=1240424348297785728, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, language=CN, label=表1, caption=

治疗前及治疗失败感染者的人口学及亚型特征［n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
变量治疗前治疗失败变量治疗前治疗失败
性别病毒载量（copies/ml）
男性416（91.03）446（91.77）>103～104—163（33.54）
女性41（8.97）40（8.23）>104～105—200（41.15）
民族>105—123（25.31）
汉族441（96.50）445（91.56）ART启动时间（年）
少数民族16（3.50）41（8.44）≤1423（92.56）—
年龄（岁）>134（7.44）—
18～29126（27.57）84（17.28）治疗时长（年）
30～49197（43.11）257（52.88）<3—279（57.41）
≥50134（29.32）145（29.84）3～5—105（21.60）
婚姻状况>5～10—91（18.72）
未婚175（38.29）177（36.42）>10—11（2.26）
已婚或有配偶232（50.77）261（53.70）治疗方案
离异或丧偶50（10.94）48（9.88）TDF+3TC+EFV—306（62.96）
职业AZT/3TC+EFV—30（6.17）
农民121（26.48）211（43.42）TDF+3TC+LPV/r—27（5.56）
学生27（5.91）14（2.88）BIC/FTC/TAF—16（3.29）
其他职业309（67.61）261（53.70）TDF+3TC+DTG—15（3.09）
感染途径其他—92（18.93）
同性性传播345（75.49）362（74.49）亚型
异性性传播109（23.85）111（22.84）CRF01_AE206（45.08）230（47.33）
其他3（0.66）13（2.67）CRF07_BC181（39.61）162（33.33）
CD4+T细胞计数（个/μl）B27（5.91）60（12.35）
<200108（23.63）194（39.92）URFs12（2.63）10（2.06）
200～500299（65.43）192（39.51）其他31（6.78）a24（4.94）b
>50050（10.94）100（20.58）合计457（100.00）486（100.00）
), ArticleFig(id=1240424348499112327, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, language=EN, label=Table 2, caption=

Frequency of drug resistance mutations among ART naive and ART failure

, figureFileSmall=null, figureFileBig=null, tableContent=
突变位点突变频数（率/%）突变位点突变频数（率/%）
治疗前治疗失败治疗前治疗失败
PIsNNRTIs
Q58E8（1.75）3（0.62）V179D/E13（2.84）81（16.67）
M46I3（0.66）0V106I/M13（2.84）38（18.72）
L10F1（0.22）2（0.41）K103N/S11（2.41）84（18.11）
I47V01（0.21）E138G/A5（1.09）11（2.26）
L90M01（0.21）G190A/S2（0.44）70（14.40）
I54V01（0.21）K101E/P1（0.22）36（7.41）
L76V01（0.21）P225H1（0.22）14（2.88）
NRTIsF227L1（0.22）11（2.26）
M184V/I4（0.88）121（24.90）H221Y1（0.22）10（2.06）
D67N/G/E2（0.44）31（6.38）M230I/L1（0.22）5（1.03）
L74I/V1（0.22）12（2.47）Y181C051（10.49）
T215I/Y/F1（0.22）10（2.06）V108I013（2.67）
K65R071（14.61）Y188L/C09（1.85）
K70E/N/T/R055（11.32）L100I07（1.44）
S68G/N055（11.32）A98G04（0.82）
Y115F034（7.00）N348I02（0.41）
K219E//NQ016（3.29）
A62V014（2.88）
V75I/M/A09（1.85）
T69del02（0.41）
), ArticleFig(id=1240424348612358541, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, language=CN, label=表2, caption=

治疗前及治疗失败感染者耐药位点突变频率

, figureFileSmall=null, figureFileBig=null, tableContent=
突变位点突变频数（率/%）突变位点突变频数（率/%）
治疗前治疗失败治疗前治疗失败
PIsNNRTIs
Q58E8（1.75）3（0.62）V179D/E13（2.84）81（16.67）
M46I3（0.66）0V106I/M13（2.84）38（18.72）
L10F1（0.22）2（0.41）K103N/S11（2.41）84（18.11）
I47V01（0.21）E138G/A5（1.09）11（2.26）
L90M01（0.21）G190A/S2（0.44）70（14.40）
I54V01（0.21）K101E/P1（0.22）36（7.41）
L76V01（0.21）P225H1（0.22）14（2.88）
NRTIsF227L1（0.22）11（2.26）
M184V/I4（0.88）121（24.90）H221Y1（0.22）10（2.06）
D67N/G/E2（0.44）31（6.38）M230I/L1（0.22）5（1.03）
L74I/V1（0.22）12（2.47）Y181C051（10.49）
T215I/Y/F1（0.22）10（2.06）V108I013（2.67）
K65R071（14.61）Y188L/C09（1.85）
K70E/N/T/R055（11.32）L100I07（1.44）
S68G/N055（11.32）A98G04（0.82）
Y115F034（7.00）N348I02（0.41）
K219E//NQ016（3.29）
A62V014（2.88）
V75I/M/A09（1.85）
T69del02（0.41）
), ArticleFig(id=1240424348729799063, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, language=EN, label=Table 3, caption=

Analysis of drug resistance influencing factors among ART naive and ART failure

, figureFileSmall=null, figureFileBig=null, tableContent=
变量治疗前治疗失败
耐药率（%）OR（95%CI）耐药率（%）OR（95%CI）
性别
男性9.13（38/416）1.00048.43（216/446）1.000
女性9.76（4/41）1.152（0.355～6.878）27.50（11/40）0.473（0.187～1.199）
民族
汉族9.30（41/441）1.00047.64（212/445）1.000
少数民族6.25（1/16）0.485（0.055～4.262）36.59（15/41）0.589（0.276～1.258）
年龄（岁）
18～2914.29（18/126）1.00035.71（30/84）1.000
30～498.12（16/197）0.727（0.294～1.800）51.36（132/257）1.803（0.909～3.573）
≥505.97（8/134）0.563（0.160～1.986）44.83（65/145）1.117（0.476～2.623）
婚姻状况
未婚13.71（24/175）1.00044.07（78/177）1.000
已婚或有配偶6.90（16/232）0.568（0.212～1.521）46.36（121/261）1.629（0.903～2.937）
离异或丧偶4.00（2/50）0.314（0.061～1.622）58.33（28/48）1.804（0.781～4.170）
职业
农民9.92（12/121）1.00039.81（84/211）1.000
学生11.11（3/27）0.538（0.115～2.504）42.86（6/14）2.256（0.569～8.938）
其他8.74（27/309）0.613（0.275～1.366）52.49（137/261）1.787（1.129～2.830）*
感染途径
同性性传播9.57（33/345）1.00048.07（174/362）1.000
异性性传播8.26（9/109）0.777（0.276～2.189）41.44（46/111）0.767（0.433～1.360）
其他0（0/3）-53.85（7/13）1.004（0.269～3.751）
CD4+T细胞计数（个/μl）
<2008.70（26/299）1.00061.86（120/194）1.000
200～5008.33（9/108）1.107（0.474～2.585）41.15（79/192）0.382（0.236～0.618）*
>50014.00（7/50）1.926（0.620～5.985）28.00（28/100）0.158（0.083～0.299）*
病毒载量（copies/ml）
>103～104——47.85（78/163）1.000
>104～105——46.50（93/200）0.757（0.456～1.257）
>105——45.53（56/123）0.701（0.392～1.253）
ART启动时间（年）
≤18.04（34/423）1.000——
>123.53（8/34）3.007（1.185～7.633）*——
治疗时长（年）
<3——39.78（111/279）1.000
3～5——58.10（61/105）2.440（1.422～4.185）*
>5～10——53.85（49/91）1.475（0.827～2.631）
>10——54.55（6/11）2.201（0.511～9.469）
治疗方案
TDF+3TC+EFV——50.00（153/306）1.000
AZT/3TC+EFV——50.00（15/30）1.008（0.405～2.509）
TDF+3TC+LPV/r——25.93（7/27）0.229（0.083～0.629）*
BIC/FTC/TAF——6.25（1/16）0.064（0.008～0.534）*
TDF+3TC+DTG——53.33（8/15）1.199（0.368～3.913）
其他——46.74（43/92）0.723（0.423～1.235）
基因亚型
CRF01_AE6.80（14/206）1.00056.09（129/230）1.000
CRF07_BC10.50（19/181）1.731（0.808～3.709）29.01（47/162）0.398（0.245～0.647）*
B7.41（2/27）1.235（0.241～6.336）58.33（35/60）1.236（0.643～2.374）
URFs8.33（1/12）1.120（0.129～9.720）20.00（2/10）0.294（0.053～1.625）
其他亚型19.35（6/31）3.227（1.043～9.991）*58.33（14/24）1.433（0.545～3.766）
), ArticleFig(id=1240424348901765535, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413926060511880, language=CN, label=表3, caption=

治疗前及治疗失败感染者耐药影响因素分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变量治疗前治疗失败
耐药率（%）OR（95%CI）耐药率（%）OR（95%CI）
性别
男性9.13（38/416）1.00048.43（216/446）1.000
女性9.76（4/41）1.152（0.355～6.878）27.50（11/40）0.473（0.187～1.199）
民族
汉族9.30（41/441）1.00047.64（212/445）1.000
少数民族6.25（1/16）0.485（0.055～4.262）36.59（15/41）0.589（0.276～1.258）
年龄（岁）
18～2914.29（18/126）1.00035.71（30/84）1.000
30～498.12（16/197）0.727（0.294～1.800）51.36（132/257）1.803（0.909～3.573）
≥505.97（8/134）0.563（0.160～1.986）44.83（65/145）1.117（0.476～2.623）
婚姻状况
未婚13.71（24/175）1.00044.07（78/177）1.000
已婚或有配偶6.90（16/232）0.568（0.212～1.521）46.36（121/261）1.629（0.903～2.937）
离异或丧偶4.00（2/50）0.314（0.061～1.622）58.33（28/48）1.804（0.781～4.170）
职业
农民9.92（12/121）1.00039.81（84/211）1.000
学生11.11（3/27）0.538（0.115～2.504）42.86（6/14）2.256（0.569～8.938）
其他8.74（27/309）0.613（0.275～1.366）52.49（137/261）1.787（1.129～2.830）*
感染途径
同性性传播9.57（33/345）1.00048.07（174/362）1.000
异性性传播8.26（9/109）0.777（0.276～2.189）41.44（46/111）0.767（0.433～1.360）
其他0（0/3）-53.85（7/13）1.004（0.269～3.751）
CD4+T细胞计数（个/μl）
<2008.70（26/299）1.00061.86（120/194）1.000
200～5008.33（9/108）1.107（0.474～2.585）41.15（79/192）0.382（0.236～0.618）*
>50014.00（7/50）1.926（0.620～5.985）28.00（28/100）0.158（0.083～0.299）*
病毒载量（copies/ml）
>103～104——47.85（78/163）1.000
>104～105——46.50（93/200）0.757（0.456～1.257）
>105——45.53（56/123）0.701（0.392～1.253）
ART启动时间（年）
≤18.04（34/423）1.000——
>123.53（8/34）3.007（1.185～7.633）*——
治疗时长（年）
<3——39.78（111/279）1.000
3～5——58.10（61/105）2.440（1.422～4.185）*
>5～10——53.85（49/91）1.475（0.827～2.631）
>10——54.55（6/11）2.201（0.511～9.469）
治疗方案
TDF+3TC+EFV——50.00（153/306）1.000
AZT/3TC+EFV——50.00（15/30）1.008（0.405～2.509）
TDF+3TC+LPV/r——25.93（7/27）0.229（0.083～0.629）*
BIC/FTC/TAF——6.25（1/16）0.064（0.008～0.534）*
TDF+3TC+DTG——53.33（8/15）1.199（0.368～3.913）
其他——46.74（43/92）0.723（0.423～1.235）
基因亚型
CRF01_AE6.80（14/206）1.00056.09（129/230）1.000
CRF07_BC10.50（19/181）1.731（0.808～3.709）29.01（47/162）0.398（0.245～0.647）*
B7.41（2/27）1.235（0.241～6.336）58.33（35/60）1.236（0.643～2.374）
URFs8.33（1/12）1.120（0.129～9.720）20.00（2/10）0.294（0.053～1.625）
其他亚型19.35（6/31）3.227（1.043～9.991）*58.33（14/24）1.433（0.545～3.766）
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河北省HIV-1感染者治疗前耐药及获得性耐药特征分析
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刘萌 , 王莹莹 , 安宁 , 白广义 , 李岩 , 徐雪昂 , 张玉琪 , 路新利
现代预防医学 | 疾病预防控制 2025,52(15): 2860-2865
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现代预防医学 | 疾病预防控制 2025, 52(15): 2860-2865
河北省HIV-1感染者治疗前耐药及获得性耐药特征分析
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刘萌, 王莹莹, 安宁, 白广义, 李岩, 徐雪昂, 张玉琪, 路新利
作者信息
  • 河北省疾病预防控制中心性病艾滋病防治所，河北省传染病病原学鉴定分析与流行病学重点实验室，河北 石家庄 050021

    • 刘萌（1991—），女，硕士，主管技师，研究方向：艾滋病防控

通讯作者:

路新利，E-mail:
Pre-treatment and acquired drug resistance characteristics among HIV-1-infected individuals in Hebei Province, China
Meng LIU, Ying-ying WANG, Ning AN, Guang-yi BAI, Yan LI, Xue-ang XU, Yu-qi ZHANG, Xin-li LU
Affiliations
  • Department of STD and AIDS Research, Hebei Provincial Center for Disease Control and Prevention, Hebei Key Laboratory of Pathogen and Epidemiology of Infectious Disease, Shijiazhuang, Hebei Province 050021, China
出版时间: 2025-08-10 doi: 10.20043/j.cnki.MPM.202503276
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摘要
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目的

了解河北省治疗前耐药（pre-treatment drug resistance，PDR）和获得性耐药（acquired drug resistance，ADR）流行情况及耐药影响因素。

方法

分别抽取2022年1月—2023年12月河北省治疗前和治疗失败HIV-1感染者的血浆样本进行耐药特征的判定，多因素logistic回归进行耐药影响因素分析。

结果

河北省PDR总体流行率为9.19%，处于中度流行态势；河北省ADR总体流行率为46.71%，ADR耐药率高且多呈现高度耐药，多重耐药现象。Logistic回归分析显示：确诊后超过1年启动抗逆转录病毒治疗（antiretroviral therapy，ART）（OR=3.007，95%CI：1.185～7.633）以及感染非CRF07_BC、B、URFs外的其他亚型（OR=3.227，95%CI：1.043～9.991）是PDR的危险因素；非农民职业（OR=1.787，95%CI：1.129～2.830）、治疗时长在3～5年（OR=2.440，95%CI：1.422～4.185）是ADR的危险因素，CD4+T淋巴细胞计数水平在200～500个/μl之间以及在500个/μl以上（OR=0.382，95%CI：0.236～0.618；OR=0.158，95%CI：0.083～0.299）、包含LPV/r或BIC的二线治疗方案（OR=0.229，95%CI：0.083～0.629；OR=0.064，95%CI：0.008～0.534）、CRF07_BC（OR=0.398，95%CI：0.245～0.647）是ADR的保护因素。

结论

发现即治疗的大背景下，应加强对当地PDR和ADR水平的监测，尽早发现耐药的流行情况，针对性采取措施降低HIV-1耐药毒株的传播，实施高质量的精准干预治疗。

HIV-1  /  治疗前耐药  /  获得性耐药  /  基因亚型
Objective

To investigate the epidemiology and influencing factors of pre-treatment drug resistance (PDR) and acquired drug resistance(ADR) in Hebei Province.

Methods

Plasma samples were collected from HIV-1-infected individuals who were ART-naive or experiencing ART failure in Hebei Province from January 2022 to December 2023 to determine drug resistance profiles. Multivariate logistic regression was used to analyze the influencing factors of drug resistance.

Results

The overall prevalence of PDR were 9.19%, showing a moderate prevalence trend. The overall prevalence of ADR was 46.71%,presenting a high level of drug resistance and the phenomenon of cross drug resistance. Multivariate logistic regression analysis showed that start ART more than one year after diagnosis (OR=3.007, 95% CI: 1.185-7.633) and being infected with subtypes other than CRF07_BC, subtype B, and URFs (OR=3.227, 95% CI: 1.043-9.991) were risk factors for PDR. Non-farmer occupation(OR=1.787, 95% CI: 1.129-2.830) and 3-5 years treatment duration(OR=2.440, 95% CI: 1.422-4.185) were risk factors for ADR, while CD4+T-cell counts between 200-500 cells/μl (OR=0.382, 95% CI: 0.236-0.618) and above 500 cells/μl(OR=0.158, 95% CI: 0.083-0.299), second-line regimens containing LPV/r or BIC (OR=0.229, 95% CI: 0.083-0.629; OR=0.064,95% CI: 0.008-0.534), and CRF07_BC(OR=0.398, 95% CI: 0.245-0.647) were protective factors for ADR.

Conclusion

Monitoring of local PDR and ADR should be strengthened to know about the situation of drug resistance as early as possible, and targeted interventions should be taken to reduce the spread of HIV-1 drug-resistant strains.

HIV-1  /  Pre-treatment drug resistance  /  Acquired drug resistance  /  Subtype
刘萌, 王莹莹, 安宁, 白广义, 李岩, 徐雪昂, 张玉琪, 路新利. 河北省HIV-1感染者治疗前耐药及获得性耐药特征分析. 现代预防医学, 2025 , 52 (15) : 2860 -2865 . DOI: 10.20043/j.cnki.MPM.202503276
Meng LIU, Ying-ying WANG, Ning AN, Guang-yi BAI, Yan LI, Xue-ang XU, Yu-qi ZHANG, Xin-li LU. Pre-treatment and acquired drug resistance characteristics among HIV-1-infected individuals in Hebei Province, China[J]. Modern Preventive Medicine, 2025 , 52 (15) : 2860 -2865 . DOI: 10.20043/j.cnki.MPM.202503276
正文
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我国自2003年实施“四免一关怀”政策以来，抗逆转录病毒治疗（antiretroviral therapy，ART）已成为艾滋病防控的有效手段。截至2023年底，全球约有HIV感染者3 990万人，约3 070万人接受抗病毒治疗[1]，但由于HIV高度变异性和药物选择压力共同作用，HIV耐药株不断出现，使ART治疗效果下降。治疗前耐药（pre-treatment drug resistance，PDR）指的是HIV-1感染者初始或再次治疗前检测到的耐药，PDR监测通过横断面研究评估所有开始抗病毒治疗患者的耐药状况，为国家制定一线ART方案提供依据。获得性耐药（acquired drug resistance，ADR）指的是由于接受ART而产生的耐药，世界卫生组织（WHO）推荐对正在接受ART且病毒载量（viral load）>1 000 copies/ml患者进行ADR监测，评估病毒抑制失败患者中HIV耐药发生和流行的程度[2]。本研究对2022—2023年河北省治疗前及治疗失败的HIV-1感染者血浆样本进行基因亚型和耐药特征的判定，了解本地区PDR及ADR形势，为本省预防HIV耐药毒株传播及建立有效耐药预警机制提供参考依据。
1　对象与方法
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1.1　研究对象
2022年1月—2023年12月，河北省治疗前HIV-1感染者和治疗失败HIV-1感染者。入组标准：（1）年龄≥18周岁；（2）人口学特征、治疗随访等基础信息完整；（3）提供知情同意书。本项目已通过河北省疾病预防控制中心伦理委员会审核（HeBCDCIRB(S)2021-029）。
1.2　研究方法
1.2.1　样本及人口学信息采集
采集符合入组要求的HIV-1感染者的外周静脉血，EDTA抗凝高速离心分离血浆，-70℃冻存待检，收集人口学信息。
1.2.2　基因型耐药检测
采用中元全自动核酸提取仪提取血浆HIV-1 RNA，通过In-house法扩增HIV-1 pol基因（1.3kb），扩增产物送德弘昌远有限公司测序。
1.2.3　序列分析
Sequencher 5.4.5对序列进行校对和拼接，Bioedit 7.0进行比对，MEGA 11.0构建邻接法系统进化树，bootstrap设为1 000次，校验值≥70%判定为同一亚型。斯坦福数据库（http://hivdb.stanford.edu）进行耐药判定，耐药程度分为高度耐药（high-level resistance，H）、中度耐药（intermediate resistance，I）、低度耐药（low-level resistance，L）、潜在耐药（potential resistance，P）和敏感（susceptibility，S）。
1.2.4　统计学分析
应用SPSS21.0软件进行数据统计分析。组间比较采用χ2检验，耐药影响因素分析采用logistic回归。检验水准α=0.05。
2　结果
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2.1　人口学特征及亚型分析
本研究共纳入457例治疗前和486例治疗失败HIV-1感染者，均以男性（91.03%、91.77%）、汉族（96.50%、91.56%）、30～49岁（43.11%、52.88%）、已婚（50.77%、53.70%）、农民（26.48%、43.42%）、同性性传播（75.49%、74.49%）为主。治疗前感染者中，CD4+T细胞计数在200～500个/μl之间的占比最高，为65.43%，92.56%感染者确诊一年内启动治疗；治疗失败感染者中，CD4+T细胞计数<200个/μl和在200～500个/μl的分别占39.92%和39.51%，病毒裁量在104～105 copies/ml之间的占41.15%，治疗0.5～3年占57.41%，治疗方案为TDF+3TC+EFV占62.96%。
HIV-1亚型以CRF01_AE（45.08%、47.33%）、CRF07_BC（39.61%、33.33%）为主，B亚型（5.91%、12.35%）、CRF55_01B（2.41%、1.23%）、CRF08_BC（2.41%、1.03%）、CRF65_cpx（0.44%、1.44%）、URFs（2.63%、2.06%）等多亚型并存。见表1。
2.2　HIV-1耐药特征分析
研究对象中，PDR发生率为9.19%（42/457）。共检出3类药物17种耐药突变位点，NNRTIs耐药位点共10种，主要为V179D/E（2.84%）、V106I/M（2.84%）等；NRTIs耐药位点4种，主要是M184V/I（0.88%）；PIs耐药位点3种，主要是Q58E（1.75%），见表2。在耐药患者中，NNRTIs耐药发生率最高，为5.69%（26/457），如NVP（5.25%），EFV（5.03%）；其次是PIs的2.41%（11/457）、NRTIs的1.75%（8/457）。多数高度耐药出现在NNRTIs耐药性突变中，PIs耐药相关基本为中度或低度耐药，如TPV/r，见图1A。
研究对象中，ADR发生率为46.71%（227/486），共检出3类药物34种耐药突变位点，NNRTIs耐药位点共16种，主要为K103N/S（18.11%）、V106I/M（10.91%）等，NRTIs耐药位点共12种，主要为M184V/I（24.90%）、K65R（14.61%）等，PIs耐药位点共6种，主要为Q58E（0.62%）等，见表2。在耐药患者中，NNRTIs耐药发生率最高，为43.21%（210/486），EFV、NVP耐药率均为42.59%；NRTIs耐药率为33.95%（165/486），ABC耐药率为33.13%，FTC、3TC均为31.89%；PIs耐药发生率最低，为1.44%（7/486）。治疗失败感染者高度耐药发生较为频繁，NNRTIs药物如NVP（41.15%）、EFV（40.74%），NRTIs药物如FTC（25.10%）、3TC（25.10%），均存在较高水平的高度耐药，见图1B。多重耐药情况同样较为频繁，有31.07%（151/486）存在多重耐药，其中NNRTIs-NRTIs双重耐药率为29.83%（145/486）。
2.3　HIV-1耐药影响因素分析
多因素非条件logistic回归分析结果如表3所示。确诊后ART启动时间及基因亚型与PDR关联有统计学意义，确诊后超过1年启动ART（相较于确诊后1年内启动ART）耐药风险更高；感染非CRF07_BC、B、URFs外的其他亚型（相较于CRF01_AE亚型）耐药风险更高。
职业、CD4+T淋巴细胞计数、治疗时长、治疗方案、基因亚型与ADR关联有统计学意义，其他职业（相较于农民）耐药发生风险更高；CD4+T淋巴细胞计数在200～500个/μl以及500个/μl以上（相较于CD4+T淋巴细胞计数在200个/μl以下）耐药风险更低；抗病毒治疗时长在3～5年（相较于抗病毒治疗时长<3年）耐药风险更高；治疗方案选择TDF+3TC+LPV/r、BIC/FTC/TAF（相较于TDF+3TC+EFV）耐药发生风险更低；CRF07_BC（相较于CRF01_AE）耐药发生风险更低。
3　讨论
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本研究对河北省2022—2023年治疗前及治疗失败HIV-1感染者人口学特征、基因亚型、耐药性进行了系统研究，两类人群均以男性、汉族、青壮年（18～49岁）为主，同性性传播是最主要的传播途径。HIV-1亚型结果显示，CRF01_AE和CRF07_BC是河北省目前最主要流行亚型，与河北省[3]之前结果一致，CRF01_AE首次在云南省的注射吸毒者中被鉴定出来[4]，近年来一直是我国主要流行的病毒亚型之一，具有较强的传播性、致病性；CRF07_BC自早期在吸毒人群中传播逐渐转变为在性传播人群中（尤其是MSM人群）广泛流行，在我国的流行率近年来呈显著上升[5]。除主要亚型外，河北省还存在B亚型、CRF08_BC、CRF65_cpx、URFs等十余种新型重组亚型传播，显示了河北省HIV-1遗传基因的多样性和流行形势的严峻性。
河北省PDR发生率为9.19%，处于WHO定义的中度流行形势（5%～15%）[6]，这一结果低于相邻城市北京（12.9%）、天津（13.5%）[7-8]，可能是与地区间监测人群、治疗覆盖率等差异相关。治疗前感染者中NNRTIs耐药率高于PIs及NRTIs，可能是由于NNRTIs突变的遗传屏障较低，单一点突变即可引起耐药造成的[9]，本研究中NNRTIs主要突变位点为K103N、V179D/E，NRTIs主要突变位点M184V/I、D67N，PIs主要突变位点为Q58E，与全国目前治疗前耐药主要的突变结果基本一致[10]。
河北省ADR发生率为46.71%，高于宁夏回族自治区（39.88%），低于吉林省（58.8%）、山西省（59.29%）[11-13]，提示需加强对在治患者的耐药监测，及时发现耐药并及时调整用药方案。河北省治疗失败人群中NNRTIs、NRTIs耐药发生率（43.21%、33.95%）较治疗前人群（5.69%、1.75%）有明显上升，并且高度耐药以及多重耐药显著高于治疗前人群，这可能与这两类药物作为国家免费抗病毒药物治疗手册推荐使用的一线抗病毒方案有关。耐药突变频率最高的是NRTIs类耐药位点M184V/I（24.90%），可能是受河北省频繁使用3TC（本研究3TC使用率为89.92%）作为抗病毒药物影响，M184V/I突变会产生对3TC或FTC的高度耐药，并与病毒复制适配性降低有关[14]。常见突变还包括K103N/S、K65R、V179D、V106M、Y181C、G190S等，而PIs耐药率在两类人群中无明显变化，提示患者可使用PIs药物来降低耐药的发生。
确诊后超过一年启动ART是PDR的危险因素，这一发现与国内外多项研究结果一致[15-16]，进一步证实了早发现、早治疗对控制耐药发生的积极作用。另外感染非CRF07_BC、B、URFs外的其他亚型同样是PDR的危险因素，相较于CRF01_AE，非CRF07_BC、B、URFs外的其他亚型PDR风险更高，提示我们需加强对新型重组株耐药突变位点及耐药特性分析。
职业、治疗时长、治疗方案、CD4+T淋巴细胞计数值、基因亚型与ADR相关。相较于农民，其他职业的ADR风险更高可能与该类人群治疗依从性差相关；抗逆转录病毒治疗的时长与ADR的发生率呈正相关，表明长时间治疗会使HIV-1毒株产生适应抗逆转录病毒药物的药物选择突变，造成病毒学失败，这提示疾控和医疗机构应及时监测患者的服药情况，定期随访及时发现并控制耐药情况的发生。高CD4+T淋巴细胞计数值是ADR的保护因素，这可能是由于免疫系统在未受到严重破坏的情况下HIV较难发生相关耐药突变与累积，提示应在CD4+T淋巴细胞水平高的早期开展治疗。包含LPV/r或BIC的治疗方案会降低ADR风险，提示使用包含LPV/r或BIC等蛋白酶抑制剂或整合酶抑制剂的抗病毒治疗方案可降低治疗患者耐药发生；CRF07_BC相较于CRF01_AE耐药风险更低，与既往研究结果一致[11]，提示应及时监测不同亚型间耐药情况，控制HIV感染、减少耐药传播。
综上所述，在发现即治疗的大背景下，HIV-1耐药风险不容忽视，河北省需要进一步加强对当地的PDR和ADR水平的监测，尽早发现耐药的流行情况，针对性地采取相应干预措施以降低HIV-1耐药毒株的传播，实施高质量的精准干预。
基金
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  • 2022年度河北省医学科学研究课题计划(20220048)
文献
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2025年第52卷第15期
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doi: 10.20043/j.cnki.MPM.202503276
  • 接收时间：2025-03-15
  • 首发时间：2026-03-16
  • 出版时间：2025-08-10
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  • 收稿日期：2025-03-15
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2022年度河北省医学科学研究课题计划(20220048)
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    河北省疾病预防控制中心性病艾滋病防治所，河北省传染病病原学鉴定分析与流行病学重点实验室，河北 石家庄 050021

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Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
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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
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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