应答指导治疗导致三个星期后完成全部治愈口腔三重直接在

StephenW

www.natap.org

AASLD/2015: Response-guided therapy leads to complete cure after three weeks of all-oral triple-direct acting antiviral regimens in non-cirrhotic chronic hepatitis C genotype 1b Chinese subjects (SODAPI study) - (12/01/15)

"In this proof-of-concept study, all patients with chronic HCV without cirrhosis who achieved an ultrarapid virological response on triple direct-acting antiviral regimens by day 2 and received 3 weeks of treatment were cured…..Chinese patients with chronic HCV genotype 1b…..an ultrarapid virological response (plasma HCV RNA <500 IU/mL by day 2, measured by COBAS TaqMan HCV test, version 2.0). In this open-label, phase 2a, single centre study, Chinese patients with chronic HCV genotype 1b infection without cirrhosis were randomly allocated by a computer program to one of three treatment groups (sofosbuvir, ledipasvir, and asunaprevir; sofosbuvir, daclatasvir, and simeprevir; or sofosbuvir, daclatasvir, and asunaprevir) until six patients in each group (1:1:1) achieved an ultrarapid virological response (plasma HCV RNA <500 IU/mL by day 2, measured by COBAS TaqMan HCV test, version 2.0).. Patients with an ultrarapid virological response received 3 weeks of therapy. Patients who did not achieve an ultrarapid response were switched to sofosbuvir and ledipasvir for either 8 weeks or 12 weeks.

A weakness of our study is the small number of patients, and the results should be validated in larger studies…...Application of this response-guided treatment approach to patients with different ethnic backgrounds, with different genotypes, and with cirrhosis should be addressed by larger clinical studies.

In this exploratory cohort of Chinese patients with chronic genotype 1b HCV who had no cirrhosis and had a uRVR to triple direct-acting antiviral regimens, we show that these regimens are well tolerated and a 100% cure rate is achievable. This study reports the shortest treatment duration of pan-oral direct-acting antivirals used for patients with chronic HCV infection. The incidence of adverse events was low compared with other reported studies on pan-oral direct-acting antiviral agents,3, 4, 5, 6 which might be related to the shorter duration of therapy. The patients are still being followed up and no relapse or adverse events have been recorded as of March, 2016.

A substantial proportion of the enrolled individuals (18 [69%] of 26) achieved a very rapid and profound drop in plasma HCV RNA. We found that this rapid viral decline could be affected by the presence of baseline NS5A resistance-associated variants (appendix p 13). The reasons for the naturally occurring resistance-associated variants are still unknown. However, in our study, baseline resistance-associated variants did not affect SVR12 in patients, irrespective of whether they had a uRVR. Even for patients who did not have a uRVR, baseline resistance-associated variants did not affect SVR12 in patients treated for longer than 3 weeks (8 weeks or 12 weeks).

Our findings are not consistent with the concept that cure corresponds to an end of treatment viral load below a cure boundary of less than one viral particle in the extracellular body fluid (ie, 15 L), which corresponds to a concentration of about 10−4·22 IU/mL.13, 14, 31 The multiscale model predicted that none of the 18 treated patients would reach the cure boundary (appendix p 9). This finding prompts a reconsideration of whether reducing the amount of virus to less than one virion is really necessary to achieve a cure.”

StephenW

www.natap.org

AASLD / 2015：应答指导治疗导致三个星期后完成全部治愈口腔三重直接在非肝硬化的慢性丙型肝炎基因1b型中国人（SODAPI研究）作用的抗病毒治疗方案 - （15年12月1日）

“在验证的概念这项研究中，所有患者的慢性丙型肝炎肝硬化没有谁取得三重直接作用的第2天的抗病毒治疗方案，并获得全部治愈治疗3周... ..Chinese慢性HCV基因型的超快速病毒学应答1B ... ..an超速病毒学应答（血浆HCV RNA <500 IU / mL的第2天，由COBAS TaqMan探针HCV测试，2.0版本计算）。在这种开放性，2a期，单中心的研究中，中国患者的慢性丙型肝炎病毒无肝硬化基因型1b感染随机由计算机程序分配到三个治疗组之一（索非布韦，ledipasvir和asunaprevir;索非布韦，daclatasvir和simeprevir;或索非布韦，daclatasvir和asunaprevir），直到每组六例（1： 1：1）实现了超速病毒学应答（血浆HCV RNA <500国际单位/毫升由第2天，通过COBAS TaqMan探针HCV测试，2.0版）测定..患者的超速病毒学应答接收治疗3周【患者谁没有。实现了超快速的响应被切换到索非布韦和ledipasvir用于为8周或12周。

我们的研究中的一个弱点是患者的数量少，其结果应在更大规模的研究来验证......这个应答指导治疗方法的患者具有不同的种族背景，具有不同基因型的应用，以及肝硬化应解决通过更大的临床研究。

在中国慢性基因型1b的HCV谁没有肝硬化和有uRVR到三重直接作用的抗病毒治疗方案的这种探索性队列中，我们表明，这些方案的耐受性良好和100％的治愈率是可以实现的。本研究报道用于治疗慢性丙型肝炎病毒感染的泛口服直接作用抗病毒剂的最短治疗持续时间。不良事件的发生率较低的与泛口服直接作用的抗病毒剂，3，4，5，6，其可能与治疗的持续时间较短其它研究报道了比较。患者仍在随访并没有复发或不良事件已被记录为2016年3月，。

（26 18 [69％]）已登记的个体有相当比例达到血浆HCV RNA非常快速和深刻的下降。我们发现，这种病毒的迅速下降可能由基线NS5A耐药相关变异的存在（附录第13页）的影响。为天然存在的抗性相关的变体的原因仍然不明。然而，在我们的研究中，基线耐药相关的变异不影响患者SVR12，不论他们是否有一个uRVR。即使对于谁没有一个uRVR患者基线耐药相关的变体没有影响SVR12在超过3周（8周或12周）治疗的患者。

我们的研究结果是不与该固化对应于小于一的病毒颗粒在细胞外体液治愈界限以下治疗病毒载量（即，15L），其对应于约10-4的浓度的端的概念是一致的·22 IU / mL.13，14，31多尺度模型预测，没有一个18治疗的患者将达到治愈边界（附录第9页）。这一发现提示减少病毒的数量不到一病毒是否真的有必要达到治愈复议“。