不完整的阿德福韦应答患者接受替诺福韦/恩曲他滨或替诺福

StephenW

Similar evolution of hepatitis B virus quasispecies in patients with incomplete adefovir response receiving tenofovir/emtricitabine combination or tenofovir monotherapy

    Fabien Lavocat
    ,
    Paul Dény
    ,
    Christian Pichoud
    ,
    Nasser Al Hawajri
    ,
    Kathryn Kitrinos
    ,
    Katyna Borroto-Esoda
    ,
    Fabien Zoulimemail address

Received 9 October 2012; received in revised form 19 April 2013; accepted 21 May 2013. published online 04 June 2013.


Background & Aims

Adefovir (ADV) resistance mutations induce low-level cross-resistance to tenofovir in vitro. Our aim was to compare viral kinetics, nucleos(t)ide analog resistance mutations, and quasispecies (QS) evolution during therapy with tenofovir disoproxil fumarate (TDF) or emtricitabine+TDF (FTC/TDF) in selected patients with incomplete ADV responses.
Methods

Patients with chronic hepatitis B and incomplete response to ADV were randomized in a double-blind trial of TDF vs. FTC/TDF. Extensive analysis of QS evolution was performed in 17 patients through 48weeks of treatment.
Results

At week 24, 48% of patients (9/17) achieved HBV DNA undetectability (<69IU/ml) with no difference between treatment groups. ADV and/or LAM resistance mutations were detected in all 17 patients at baseline and in 5/6 analyzable patients at week 48. A total of 1224 reverse transcriptase clones were analyzed. Clonal analysis revealed no significant difference at baseline in QS complexity or diversity between treatment groups. There was a trend in both treatment groups for an increase in QS complexity at week 12, followed by a decrease in complexity and diversity by week 48. Analysis of individual patients showed no consistent selection/accumulation of specific viral resistance patterns during treatment, but at week 48, mutations at rtA181 persisted in 4 patients.
Conclusions

TDF or FTC/TDF demonstrated strong viral suppression in patients with an incomplete response to ADV and no significant selective pressure on pre-existing ADV or LAM resistant strains. TDF monotherapy and FTC/TDF combination therapy had a comparable impact on QS evolution.

StephenW

背景与目的

阿德福韦（ ADV ）耐药性突变替诺福韦在体外诱导低级别的交叉耐药性。我们的目标是比较富马酸替诺福韦（ TDF ）或恩曲他滨+ TDF （ FTC / TDF ）不全ADV响应患者在治疗过程中病毒动力学，核苷（酸）IDE模拟耐药突变，以及准种进化（ QS ） 。
方法

慢性乙型肝炎和不完整的响应ADV患者随机TDF与FTC / TDF在双盲试验。广泛QS进化分析， 17例患者中进行，通过治疗48周。
结果

在第24周， 48 ％的患者（9/17 ）达到HBV DNA不可检测（< 69IU/ml ）治疗组之间无差异。 ADV和/或LAM耐药突变检测，在所有17名患者在基线和分析的患者在48周5/6 。共有1224逆转录克隆进行了分析。克隆分析表明基线QS复杂性或多样性治疗组之间没有显着差别。 QS复杂性的增加，在第12周在48周的复杂性和多样性的减少，其次在两个治疗组有增高的趋势。个别患者的分析显示，在治疗过程中的特定病毒的耐药模式没有一致的选择/积累，但在第48周，突变在rtA181坚持4例。
结论

TDF或FTC / TDF表现出强大的抑制病毒的患者不完整的响应ADV和预先存在的ADV或林耐药菌株没有明显的选择性压力。 TDF单药治疗和FTC / TDF联合治疗有一个可比的上QS演变的影响。

齐欢畅2

FTC / TDF

齐欢畅2

恩曲他滨+ TDF （ FTC / TDF ）是当今最强的抗病毒核苷药物。

山东小兵

回复 齐欢畅2 的帖子

恩曲他滨多少钱？

齐欢畅2

不知道多少钱，暂时没得卖吧。恩曲他并原来是用于艾滋病的，作用于病毒逆转录，与乙肝有类似效应。从抗病毒角度说，联合用药比单一用药更有效。这就是鸡尾酒疗法的思路。

StephenW

据斯特拉瑟教授(Prof Simone Strasser)，来自澳大利亚的乙肝专家:
恩曲他滨是一种强效的核苷类似物, 对抗HBV和HIV有效. 作为单药治疗时，耐药性高, 因此，它总是与其他抗病毒组合使用.
现在，TRUVADA（替诺福韦+恩曲他滨）是FDA批准艾滋病毒治疗，但不为HBV.
据斯特拉瑟教授, 没有证据显示Truvada对单用替诺福韦有优势.


在短期内,最有希望一个更好的抗病毒药物是TAF（GS7340）
TAF是一种替诺福韦前药，产生较高的细胞和血浆浓度较低的替诺福韦二磷酸，替诺福韦的活性代谢物.

MP4

齐欢畅2 发表于 2013-9-27 00:02
不知道多少钱，暂时没得卖吧。恩曲他并原来是用于艾滋病的，作用于病毒逆转录，与乙肝有类似效应。从抗病毒 ...

恩曲他滨
和混合片都有得卖

齐欢畅2

那我不知道了，应该有更好的效果吧。联合用药。
用于艾滋病治疗，现在国内有卖的了吧。