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首页> 外文期刊>Antiviral therapy >Clonal analysis of the quasispecies of antiviralresistant HBV genomes in patients with entecavir resistance during rescue treatment and successful treatment of entecavir resistance with tenofovir
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Clonal analysis of the quasispecies of antiviralresistant HBV genomes in patients with entecavir resistance during rescue treatment and successful treatment of entecavir resistance with tenofovir

机译:恩替卡韦耐药患者在抢救治疗期间成功耐药的乙肝病毒基因组的克隆分析以及替诺福韦成功治疗恩替卡韦耐药的患者

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Background: Clonal analysis of quasispecies of resistant HBV genomes in patients with entecavir (ETV) resistance receiving lamivudine (3TC) plus adefovir (ADV) rescue therapy has never been performed. Methods: A sample of 10 patients with ETV resistance who were switched to 3TC+ADV treatment were analysed for changes in viral quasispecies. Serum samples at baseline, and at months 3 and 6 of 3TC+ADV treatment could be clonally analysed in 7 of 10 patients; 3-82 clones per sample (total 1,068 clones, mean 63) were sequenced. Results: 3TC+ADV therapy led to a modest decline in HBV DNA. Almost all clones had L180M and M204V 3TC resistance mutations before and during combination therapy. All clones had ??1 of the S202G, T184F, T184A, T184L, T184I and M250V ETV resistance mutations. The percentages of detected clones bearing 3TC (rtL180M and rtM204V) and ETV mutations did not change with rescue 3TC+ADV therapy. In 7 of 8 patients with detectable HBV DNA (median 5.17 log 10 copies/ml) after a median 24 months of ADV therapy, HBV DNA became undetectable with 3TC plus tenofovir after 6 months of treatment. Conclusions: In patients with ETV resistance tenofovir is effective. Clonal analysis data indicate no selection of speciic HBV mutants during rescue 3TC+ADV. ? 2013 International Medical Press.
机译:背景:从未接受过接受拉米夫定(3TC)加阿德福韦酯(ADV)抢救治疗的恩替卡韦(ETV)耐药患者的耐药乙肝病毒基因组准种的克隆分析。方法:分析10例接受ETV耐药的患者,他们改用3TC + ADV治疗,以分析病毒准种的变化。可以对10例患者中的7例进行基线分析,以及3TC + ADV治疗第3和6个月时的血清样本。每个样品中有3-82个克隆(总共1,068个克隆,平均63个)进行了测序。结果:3TC + ADV治疗导致HBV DNA适度下降。在联合治疗之前和期间,几乎所有克隆均具有L180M和M204V 3TC耐药性突变。所有克隆均具有S202G,T184F,T184A,T184L,T184I和M250V ETV抗性突变的Δ1。救援3TC + ADV疗法检测到的带有3TC(rtL180M和rtM204V)和ETV突变的克隆的百分比没有变化。在中位ADV治疗24个月后,有8例可检测到HBV DNA(中位数为5.17 log 10拷贝/ ml)的患者中有7例在治疗6个月后用3TC加替诺福韦检测不到HBV DNA。结论:在ETV耐药的患者中,替诺福韦有效。克隆分析数据表明在抢救3TC + ADV期间没有选择特定的HBV突变体。 ? 2013国际医学出版社。

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