Differential analysis of genotype drug resistance in 576 HIV/AIDS patients who failed treatment with a zidovudine-containing or tenofovir-containing regimen in Yunnan Province
PAN Xiao-man1,2, LI Jian-jian2, ZHANG Mi2, LIU Jia-fa2, YANG Cui-xian2, YANG Bi-hun2, DONG Xing-qi1,2
1. School of Public Health, Kunming Medicine University, Kunming, Yunnan 650000, China; 2. Yunnan Provincial Infectious Disease Hospital, Yunnan AIDS Care Center, Kunming, Yunnan 650301, China
Abstract：Objective To compare the differences in genotype drug resistance mutations in patients who failed treatment with a zidovudine(AZT)-containing or tenofovir(TDF)-containing regimen, and to explore the related influencing factors. Methods We collected the information about patients with first-line antiretroviral regimens for more than six months as well as positive results in genotypic antiretroviral drug resistance testing.Univariate testing was used to determine the variables associated with AZT or TDF resistance, and multiple correspondence analysis was performed to obtain the correlation of variables. Results Among 576 patients treated with an AZT-containing regimen or a TDF-containing regimen, the common drug-resistant mutations were M184V/I, D67N, K70R/E/Q, K65R and T69N. Univariate analysis showed that drug-resistant mutations in the patients receiving the above-mentioned two drugs were not correlated with the patients' age (χ2=3.503, P=0.320) and pathways of infection (χ2=3.122, P=0.210), but correlated with mutation sites (χ2=104.438, P=0.000), virus load (χ2=17.284, P=0.000), CD4+ T lymphocytes (χ2=33.338, P=0.000), gender (χ2=8.904, P=0.003) and duration of treatment (χ2=40.081, P=0.000). Multiple correspondence analysis showed that drug-resistant mutation induced by receiving an AZT-containing regimen was correlated with treatment duration more than 2 years (25 months), virus load < 10,000 copies/ml and CD4+ T lymphocyte count ≥200 cells/mm3, while drug-resistant mutation induced by receiving a TDF-containing regimen showed aggregation with treatment duration within 2 years (0-24 months), virus load ≥ 10,000 copies/ml, CD4+ T lymphocyte count <200 cells/mm3 and K65R. Conclusions Multiple correspondence analysis is extremely suitable for studying HIV-resistant demographics and mutations.M184V/I drug-resistant mutation is correlated with D67N and K70R/E/Q. As compared with the TDF-containing regimen,common mutations in NRTIs are mainly induced by the AZT-containing regimen. T69N and AZT resistance is associated with low virus load. As for long-term use of an AZT-containing regimen, genotypic drug resistance should be closely monitored. With regard to receiving a TDF-containing regimen, virus load and CD4+ T lymphocyte count should be actively monitored in the early stage.
潘小满, 李健健, 张米, 刘家法, 杨翠先, 杨壁珲, 董兴齐. 云南省576例齐多夫定或替诺福韦方案治疗失败的HIV/AIDS患者基因型耐药差异性分析[J]. 实用预防医学, 2020, 27(12): 1412-1416.
PAN Xiao-man, LI Jian-jian, ZHANG Mi, LIU Jia-fa, YANG Cui-xian, YANG Bi-hun, DONG Xing-qi. Differential analysis of genotype drug resistance in 576 HIV/AIDS patients who failed treatment with a zidovudine-containing or tenofovir-containing regimen in Yunnan Province. , 2020, 27(12): 1412-1416.
[1] Clutter DS, Jordan MR, Bertagnolio S, et al. HIV-1 drug resistance and resistance testing [J].Infect Genet Evol, 2016,46:292-307. [2] Mutasa-Apollo T, Ford N, Wiens M, et al. Effect of frequency of clinic visits and medication pick-up on antiretroviral treatment outcomes:a systematic literature review and meta-analysis [J].J Int AIDS Soc, 2017, 20(Suppl 4):21647. [3] AIDSMAP.Drug resistance[EB/OL].[2017-10-03](2019-11-20).http://www.aidsmap.com/resources/treatmentsdirectory/Drug-resis-tance/page/1280050/. [4] 龙茂娇,李健健,董兴齐.HIV基因型耐药检测在抗病毒治疗中的应用进展[J].国际流行病学传染病学杂志,2017,44(5):333-337. [5] 杨绍敏,钟敏,杨壁珲,等.云南省2008—2012年HIV-1耐药基因型检测情况[J].中国艾滋病性病,2014,20(1):9-12,26. [6] 中国疾病预防控制中心, 性病艾滋病预防控制中心.国家免费艾滋病抗病毒药物治疗手册[M].第4版.北京:人民卫生出版社,2016. [7] 张春阳,王征桦,颜苹苹.福建省AIDS患者抗病毒疗效及流行病学特征[J].海峡预防医学杂志,2016,22(6):19-21. [8] Gagliardini R, Ciccullo A, Borghetti A, et al. Impact of the M184V resistance mutation on virological efficacy and durability of lamivudine-based dual antiretroviral regimens as maintenance therapy in individuals with suppressed HIV-1 RNA: a cohort study[J].Open Forum Infect Dis, 2018,5(6):ofy113. [9] 吴守丽,刘峰,颜苹苹,等.HIV-1耐药突变的研究进展[J].中国人兽共患病学报,2018,34(1):44-53. [10] Telwatte S, Hearps AC, Johnson A, et al. Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations[J].Nucleic Acids Res, 2015,43(6):3256-3271. [11] Xu HT, Colby-Germinario SP, Quashie PK, et al. Subtype-specific analysis of the K65R substitution in HIV-1 that confers hypersusceptibility to a novel nucleotide-competing reverse transcriptase inhibitor[J].Antimicrob Agents Chemother, 2015,59(6):3189-3196. [12] 李敬云. HIV的耐药基因突变[J].中国艾滋病性病, 2010,16(2):195-200. [13] Henrich TJ, Hatano H, Bacon O, et al. HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: an observational study[J]. PLoS Med, 2017,14(11):e1002417. [14] 李强,李杰,桑锋,等.HIV感染者和AIDS患者外周血T淋巴细胞活化亚群与病毒载量的相关性[J].中国全科医学, 2016,19(8):869-872. [15] 姚刚, 朱克京, 杜曼, 等.珠海市艾滋病患者高效抗逆转录病毒治疗免疫学效果及影响因素分析[J].实用预防医学,2018,25(3):294-297. [16] Liu F, Fan X, Auclair S, et al. Sequential dysfunction and progressive depletion of Candida albicans-specific CD4 T cell response in HIV-1 infection[J].PLoS Pathog, 2016,12(6):e1005663. [17] 杨翠先. 中国云南省HIV/AIDS患者基因变异与耐药的研究[D].重庆:第三军医大学,2015. [18] 种雪静,戴国瑞,杨涤,等.HIV/AIDS病人一线ART药物治疗失败发生时间的分析[J].中国艾滋病性病,2016,22(10):772-775.
2020, Vol. 27 
