恩替卡韦和替诺福韦: 耐药不再是一个问题

StephenW

Resistance is no Longer a Problem with Entecavir and Tenofovir

    Seng Gee Lim,
    Guan Huei Lee,
    Kieron Lim,
    Poh Seng Tan


Abstract

The treatment of chronic hepatitis B has been transformed with the advent of nucleos(t)ide analogues. With this came the recognition of viral resistance which was defined as rebound of viral HBV DNA >1 log from nadir associated with genotypic mutations of viral resistance. Resistance was associated with loss of efficacy, with the clinical consequences of viral relapse, reactivation of chronic hepatitis B, increased risk of hepatitis B flares, liver decompensation, and increased mortality especially in cirrhotic patients. Resistance rates varied between different nucleos(t)ide analogues and were generally classified as low or high genetic barrier to resistance. Different pathways to development of viral resistance were recognized, with therapeutic options for rescue therapy determined by such pathways. The two high genetic barrier drugs, entecavir and tenofovir showed remarkably low or absence of viral resistance in treatment naïve patients over 5 years or longer of therapy. However in treatment-experienced patients, particularly those with viral resistance, results were less optimal. For entecavir, prior lamivudine resistance conferred an entecavir resistance rate of 43 % over 5 years while with tenofovir, although resistance did not seem apparent, patients with prior adefovir resistance had suboptimal responses to tenofovir therapy. In cases of multiresistant hepatitis B virus defined as resistance to at least two nucleos(t)ide analogues in the same viral strain, rescue with a combination of tenofovir and entecavir appeared highly efficacious. Consequently, the optimistic view that these new drugs lead to absence of resistance needs to be tempered by the larger burden of drug experienced and drug resistant patients compared to treatment naïve patients. Furthermore, it is unclear whether resistance may be a concern with high genetic barrier drugs after one or two decades of therapy. In time, it is possible that with the increasing use of high genetic barrier drugs, viral resistance will be a lesser problem, but unlikely to disappear completely

StephenW

慢性B型肝炎的治疗已转化与核苷（酸）类似物的问世。有了这个来识别病毒耐药病毒HBV DNA被定义为反弹，从最低点的1日志相关的基因型病毒耐药突变。性是与失去疗效，病毒复发的临床后果，重新慢性乙型肝炎，乙肝耀斑，肝功能失代偿的风险增加，尤其是肝硬化患者的死亡率增加。之间变化不同的核苷（酸）类似物耐药率一般归类为低或高耐药基因屏障。不同的病毒耐药性的发展途径进行确认，抢救治疗等途径确定治疗方案。两高基因屏障的药物，恩替卡韦和替诺福韦表现出非常低或没有在初次接受治疗的患者超过5年或更长的治疗病毒性。然而，在治疗经验的患者，特别是那些与病毒耐药，疗效达不到最佳。恩替卡韦，拉米夫定耐药之前赋予43％的恩替卡韦的耐药率超过5年，而替诺福韦，但阻力似乎并不明显，前阿德福韦耐药的患者替诺福韦治疗反应欠佳的。例多重耐药性的B型肝炎病毒的电阻定义为至少两个核苷类似物（t）的拯救的组合，替诺福韦，恩替卡韦，出现在相同的病毒株，高度有效的。因此，乐观的看法，这些新药物无耐药性导致更大的负担，初次接受治疗的患者相比，经验丰富的药物和耐药患者需要得到锻炼。此外，目前还不清楚是否电阻具有高基因屏障的药物治疗一，二十年后可能是一个关注。随着时间的推移，它是可能的，随着越来越多地使用的高基因屏障的药物，病毒性将是一个较小的问题，但不可能完全消失.

诗意栖居

是否可以这样理解，这是一个很早以前的报道，大意是说相比于拉米夫定，恩替卡韦和替诺福韦耐药率很低，并展望了一下美好的未来。

StephenW

诗意栖居 发表于 2013-6-5 09:17
是否可以这样理解，这是一个很早以前的报道，大意是说相比于拉米夫定，恩替卡韦和替诺福韦耐药率很低，并展 ...

消息是：开始治疗,用高基因屏障(针对耐药)的药物，病毒性耐药将是一个较小的问题，但不可能完全消失.

tongkong

换句话说，我们的命在他们的手里。。。。。。