Background & Aims

The combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is recommended for the retreatment of patients with HCV infection in whom previous direct-acting antiviral (DAA) treatment failed. However, whether ribavirin further increases the therapeutic efficacy of SOF/VEL/VOX retreatment remains unclear. We aimed to test this hypothesis in a randomized-controlled trial.

Methods

We randomly assigned 315 patients with DAA treatment failure from five Egyptian sites into two groups. Group A (n = 158) received SOF/VEL/VOX for 12 weeks, and group B (n = 157) received SOF/VEL/VOX + weight-based ribavirin for 12 weeks. Therapeutic efficacy was defined as SVR12 (sustained virologic response 12 weeks after treatment end). Safety and tolerability were evaluated by monitoring treatment-related adverse events (AEs) and laboratory abnormalities.

Results

Males comprised 53.9% of group A and 57.1% of group B (p = 0.58); mean ages were 51.8 and 47.3 years in group A and B, respectively. Seventeen patients in each group were lost to follow-up. SVR12 rates were 87.3% (138/158) by intention-to-treat analysis and 97.8% (138/141) by per-protocol analysis in group A; and 87.9% (138/157) and 98.5% (138/140), respectively, in group B (p = n.s. for intention-to-treat and per-protocol analyses). Both regimens were well-tolerated, with no deaths and only one serious AE (anemia) in group B, which required ribavirin discontinuation. Fifty-five patients in group A vs. 77 in group B experienced any AE (p = 0.002).

Conclusion

This randomized-controlled trial showed equal, high efficacy of both regimens for the retreatment of previous DAA failures, although ribavirin was associated with more AEs. Therefore SOF/VEL/VOX monotherapy should be the preferred retreatment strategy.

ClincialTrials.gov number

NCT04695769.

Impact and implications

HCV treatment guidelines recommend retreatment of direct-acting antiviral (DAA) treatment failures with the combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) for 12 weeks. However, whether ribavirin exerts an additional/synergistic effect remains unclear. The present study confirmed that SOF/VEL/VOX without ribavirin is the best regimen for retreatment of DAA treatment failures, and thus will help guide clinicians caring for patients who are not cured with a first course of DAA therapy.

中文翻译：

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SOF/VEL/VOX联合或不联合利巴韦林再治疗慢性丙型肝炎的随机对照试验

背景与目标

建议将索磷布韦、维帕他韦和伏西拉瑞韦 (SOF/VEL/VOX) 联合用于既往直接抗病毒 (DAA) 治疗失败的 HCV 感染患者的再治疗。然而，利巴韦林是否进一步提高 SOF/VEL/VOX 复治的疗效仍不清楚。我们旨在通过随机对照试验检验这一假设。

方法

我们将来自埃及 5 个地点的 315 名 DAA 治疗失败患者随机分为两组。A 组 (n = 158) 接受 SOF/VEL/VOX 治疗 12 周，B 组 (n = 157) 接受 SOF/VEL/VOX + 基于体重的利巴韦林治疗 12 周。治疗效果定义为 SVR12（治疗结束后 12 周的持续病毒学应答）。通过监测治疗相关的不良事件（AE）和实验室异常来评估安全性和耐受性。

结果

A 组中男性占 53.9%，B 组中男性占 57.1% ( p  = 0.58)；A组和B组的平均年龄分别为51.8岁和47.3岁。每组有 17 名患者失访。根据意向治疗分析，A 组的 SVR12 率为 87.3% (138/158)，根据方案分析，A 组的 SVR12 率为 97.8% (138/141)；B 组分别为 87.9% (138/157) 和 98.5% (138/140)（ 对于意向治疗和符合方案分析，p = ns）。两种治疗方案均具有良好的耐受性，B 组没有死亡，只有 1 例严重 AE（贫血），需要停用利巴韦林。A 组有 55 名患者出现任何AE，而 B 组有 77 名患者出现任何 AE ( p  = 0.002)。

结论

这项随机对照试验显示，尽管利巴韦林与更多 AE 相关，但两种方案对于先前 DAA 失败的再治疗具有相同的高效效果。因此SOF/VEL/VOX单一疗法应该是首选的再治疗策略。

ClincialTrials.gov 编号

NCT04695769。

影响和影响

HCV 治疗指南建议对直接作用抗病毒 (DAA) 治疗失败的患者使用索磷布韦、维帕他韦和伏西拉瑞韦 (SOF/VEL/VOX) 组合进行 12 周的再治疗。然而，利巴韦林是否发挥额外/协同作用仍不清楚。本研究证实，不含利巴韦林的 SOF/VEL/VOX 是 DAA 治疗失败再治疗的最佳方案，因此将有助于指导临床医生治疗第一个疗程 DAA 治疗未治愈的患者。