Hamburg, Germany.
New York City, NY, USA.
Aliment Pharmacol Ther. 2018 May;47(9):1288-1295. doi: 10.1111/apt.14592. Epub 2018 Mar 14.
Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response.
To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting.
In this multicentre cohort study, GT3 patients from ten treatment centres across Germany were included. Sustained virological response was assessed 12 weeks after end-of-treatment (SVR12) in modified intention-to-treat (mITT) and per-protocol analysis (PP). NS5A RASs were tested by population-based sequencing.
A total of 293 GT3 patients were included. The median age was 48 years, 70% were male, 25.3% were cirrhotic, 9.2% were HCV/HIV co-infected and 21.8% were treatment-experienced, including 4.1% with DAA experience. Baseline NS5A RASs (Y93H, A30K, L31M) were detected in 11.2%. RBV was added in 5% of noncirrhotic and 58.9% of cirrhotic patients, respectively. SVR12 rates for SOF/VEL±RBV were 95.9% (mITT) and 99.5% (PP), respectively. Only 1 virological relapse occurred in a cirrhotic patient previously treated with SOF/RBV. No treatment-related major adverse events occurred.
Twelve weeks of SOL/VEL±RBV was safe and highly efficient in HCV GT3 across a diverse patient population. Baseline NS5A RASs were rarely observed and presence did not seem to impact SVR, regardless of the use of RBV.
在 ASTRAL-3 批准研究中，12 周的泛基因型直接作用抗病毒（DAA）联合索磷布韦/维帕他韦（SOF/VEL）治疗丙型肝炎病毒（HCV）基因型 3（GT3）感染患者的疗效非常高。然而，HCV 非结构蛋白 5A（NS5A）中存在耐药相关取代（RAS）与较低的治疗反应相关。
在真实环境中评估 SOF/VEL±利巴韦林（RBV）在 HCV GT3 感染中的疗效和安全性，以及 NS5A RAS 和 RBV 使用对治疗结果的影响。
在这项多中心队列研究中，德国十个治疗中心的 GT3 患者被纳入研究。在改良意向治疗（mITT）和方案分析（PP）中，在治疗结束后 12 周评估持续病毒学应答（SVR12）。通过基于人群的测序检测 NS5A RAS。
共纳入 293 例 GT3 患者。中位年龄为 48 岁，70%为男性，25.3%为肝硬化，9.2%为 HCV/HIV 合并感染，21.8%为治疗经验丰富的患者，包括 4.1%为 DAA 治疗经验。基线时检测到 NS5A RAS（Y93H、A30K、L31M）的患者占 11.2%。分别有 5%的非肝硬化和 58.9%的肝硬化患者加用 RBV。SOF/VEL±RBV 的 SVR12 率分别为 95.9%（mITT）和 99.5%（PP）。只有 1 例先前用 SOF/RBV 治疗的肝硬化患者发生病毒学复发。未发生与治疗相关的重大不良事件。
SOF/VEL±RBV 治疗 12 周在各种患者人群中是安全且高效的。HCV GT3 患者的基线 NS5A RAS 很少见，且无论 RBV 的使用情况如何，它们的存在似乎都不会影响 SVR。
