摘要
目的分析云南省抗病毒治疗失败的HIV感染/AIDS患者的耐药特征、演变趋势及耐药突变位点分布。方法采用横断面研究方法,收集并分析云南省2021年1月至2023年12月抗病毒治疗失败的15159例HIV感染/AIDS患者的人口学特征及基因型耐药数据。统计学分析采用χ^(2)检验。结果15159例HIV感染/AIDS患者中,扩增阳性12215例,其中流行重组型(CRF)08_BC为主要基因亚型[54.97%(6714/12215)],其次为CRF01_AE[16.14%(1972/12215)]和CRF07_BC[14.48%(1769/12215)]。HIV-1 RNA为≥200~<1000拷贝/mL时,耐药率为21.48%(99/461);HIV-1 RNA为≥1000~<10000拷贝/mL时,耐药率为51.29%(2867/5590);HIV-1 RNA为≥10000~<100000拷贝/mL时,耐药率为69.39%(3979/5734);HIV-1 RNA≥100000拷贝/mL时,耐药率为81.86%(352/430)。共检出耐药7297例,耐药率为59.74%(7297/12215),据此估算云南省抗病毒治疗人群的耐药率为2.00%(7297/364238)。2021年至2023年,患者每年耐药率分别为60.71%(2554/4207)、60.28%(1671/2772)、58.67%(3072/5236),差异无统计学意义(χ^(2)=4.47,P=0.107)。在抗病毒治疗失败人群中,非核苷类反转录酶抑制剂(NNRTI)、核苷类反转录酶抑制剂(NRTI)和蛋白酶抑制剂(PI)的耐药率分别为93.70%(6837/7297)、44.10%(3218/7297)和5.15%(376/7297)。NRTI、NNRTI和PI三类药物出现突变位点频次最高的分别为M184V/I[46.13%(2123/4602)]、K103N/S[37.14%(2648/7129)]、L33F[15.50%(82/529)]和M46I/L[15.50%(82/529)]。耐药程度分析显示,NNRTI类药物中奈韦拉平[49.01%(5987/12215)]和依非韦伦[48.00%(5863/12215)]耐药率最高,NRTI类药物中恩曲他滨[23.59%(2882/12215)]和拉米夫定[23.58%(2881/12215)]次之。结论2021年至2023年云南省抗病毒治疗失败HIV感染/AIDS患者的主要基因亚型为CRF08_BC。患者耐药率随HIV-1病毒载量升高而上升。2021年至2023年每年耐药率无显著变化。NNRTI类药物耐药率最高,NRTI次之,PI最低;主要突变位点分别为NRTI的M184V/I、NNRTI的K103N/S、PI的M46I/L和L33F;奈韦拉平、依非韦伦及恩曲他滨、拉米夫定耐药率较高。
ObjectiveTo investigate the overall drug resistance,drug resistance trend and distribution of drug resistance mutation sites in human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)patients with antiviral therapy failure in Yunnan Province.MethodsThe demographic data and genotype drug resistance of HIV/AIDS population with antiviral therapy failure in Yunnan Province from January 2021 to December 2023 were collected and analyzed by cross-sectional investigation.Statistical analyses were performed using chi-square test.ResultsAmong 15159 HIV/AIDS patients,12215 cases tested positive by amplification.The circulating recombinant form(CRF)08_BC was the predominant genetic subtype,accounting for 54.97%(6714/12215),followed by CRF01_AE(16.14%(1972/12215))and CRF07_BC(14.48%(1769/12215)).When the viral load was≥200 to<1000 copies/mL,the incidence of drug resistance was 21.48%(99/461).When it was≥1000 to<10000 copies/mL,the incidence was 51.29%(2867/5590).When it was≥10000 to<100000 copies/mL,the incidence was 69.39%(3979/5734).When it was≥100000 copies/mL,the incidence was 81.86%(352/430).A total of 7297 drug resistant cases were detected,with a drug resistance rate of 59.74%(7297/12215),thus the estimated drug resistance incidence rate among the antiviral treated population in Yunnan Province was 2.00%(7297/364238).From 2021 to 2023,the annual drug resistance rates among patients were 60.71%(2554/4207),60.28%(1671/2772),and 58.67%(3072/5236),respectively,with no statistically significant difference(χ^(2)=4.47,P=0.107).Among the population with antiviral therapy failure,the drug resistance rates of non-nucleoside reverse transcriptase inhibitor(NNRTI),nucleoside reverse transcriptase inhibitor(NRTI),and protease inhibitor(PI)were 93.70%(6837/7297),44.10%(3218/7297)and 5.15%(376/7297),respectively.The mutation sites with the highest frequencies among the three classes of drugs including NRTI,NNRTI and PI were M184V/I(46.13%(2123/4602)),K103N/S(37.14%(2648/7129)),L33F(15.50%(82/529))and M46I/L(15.50%(82/529)),respectively.Analysis of the degree of drug resistance showed that among NNRTI drugs,nevirapine(49.01%(5987/12215))and efavirenz(48.00%(5863/12215))had the highest drug resistance rates,followed by emtricitabine(23.59%(2882/12215))and lamivudine(23.58%(2881/12215))among NRTI drugs.ConclusionsAmong HIV/AIDS patients with antiviral therapy failure in Yunnan Province from 2021 to 2023,CRF08_BC is the main genetic subtype.The drug resistance rate of patients increases with the increase of HIV-1 viral load.There is no significant change in the drug resistance rate from 2021 to 2023.NNRTI has the highest drug resistance rate,followed by NRTI,and PI has the lowest.The main mutation sites are M184V/I for NRTI,K103N/S for NNRTI,and M46I/L and L33F for PI.The drug resistance rates of nevirapine,efavirenz,emtricitabine and lamivudine are relatively high.
作者
樊红丽
张米
刘家法
叶军川
李侠
王佳丽
邓雪媚
王林
马莎
李健健
Fan Hongli;Zhang Mi;Liu Jiafa;Ye Junchuan;Li Xia;Wang Jiali;Deng Xuemei;Wang Lin;Ma Sha;Li Jianjian(Department of Clinical Laboratory,Yunnan Provincial Hospital of Infectious Diseases(Affiliated Infectious Disease Hospital of Kunming Medical University),Kunming 650301,China;Science and Education Department,Yunnan Provincial Hospital of Infectious Diseases(Affiliated Infectious Disease Hospital of Kunming Medical University),Kunming 650301,China;Department of Public Health,Yunnan Provincial Hospital of Infectious Diseases(Affiliated Infectious Disease Hospital of Kunming Medical University),Kunming 650301,China;Hospital Office,Yunnan Provincial Hospital of Infectious Diseases(Affiliated Infectious Disease Hospital of Kunming Medical University),Kunming 650301,China)
出处
《中华传染病杂志》
北大核心
2025年第7期395-402,共8页
Chinese Journal of Infectious Diseases
基金
云南省科技厅-昆明医科大学应用基础研究联合专项资金资助项目(202301AY070001-282,202201AY070001-208)
云南省重大科技专项计划(202405AJ310002)
昆明医科大学艾滋病共感染传染性疾病诊疗科技创新团项目(CXTD202111)。
