Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
Expert Opin Pharmacother. 2024 Aug;25(12):1691-1706. doi: 10.1080/14656566.2024.2396024. Epub 2024 Aug 26.
Pharmacotherapy against hepatitis C virus (HCV) infection has tremendously improved since the advent of interferon (IFN)-free direct-acting antivirals (DAAs). Additionally, fixed-dose pangenotypic DAAs, which are safe, potent, easy for use, and can cover a wide spectrum of patients, have been recommended by professional guidelines for DAA-naïve and DAA-experienced patients with HCV.
We review the pharmacokinetics, pharmacodynamics, and potential drug-drug interactions (DDIs) of fixed-dose pangenotypic DAA regimens, including glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). Additionally, we summarize the efficacy and safety of these regimens in clinical trials as well as real-world studies for treating different populations. Lastly, we discuss unmet medical needs in managing HCV in the era of fixed-dose pangenotypic DAAs.
Protease inhibitors (PIs), including GLE and VOX, are prone to have more frequent DDIs, compared to the non-structural (NS) 5A and 5B inhibitors. These regimens are generally well tolerated and can be applied to different populations, except for the contraindicated use of PI-containing DAA regimens in decompensated cirrhosis. Using the first-line GLE/PIB and SOF/VEL can eradicate HCV in more than 95% of DAA-naïve patients across different populations. The viral cure usually exceeds 95% when using the rescue SOF/VEL/VOX regimen for prior DAA failures.
自无干扰素直接作用抗病毒药物（DAA）问世以来，针对丙型肝炎病毒（HCV）感染的药物治疗已经取得了巨大进展。此外，固定剂量泛基因型 DAA 因其安全、有效、使用方便，且能覆盖广泛的患者群体，已被专业指南推荐用于 DAA 初治和 DAA 经治的 HCV 患者。
我们回顾了固定剂量泛基因型 DAA 方案的药代动力学、药效学和潜在药物相互作用（DDI），包括格卡瑞韦/哌仑他韦（GLE/PIB）、索磷布韦/维帕他韦（SOF/VEL）和索磷布韦/维帕他韦/伏西瑞韦（SOF/VEL/VOX）。此外，我们总结了这些方案在临床试验和真实世界研究中治疗不同人群的疗效和安全性。最后，我们讨论了在固定剂量泛基因型 DAA 时代管理 HCV 方面尚未满足的医疗需求。
与非结构（NS）5A 和 5B 抑制剂相比，蛋白酶抑制剂（PI），包括 GLE 和 VOX，更容易发生更频繁的 DDI。这些方案通常具有良好的耐受性，可适用于不同人群，除了含 PI 的 DAA 方案在失代偿性肝硬化中的禁忌使用。使用一线 GLE/PIB 和 SOF/VEL，可在不同人群中使超过 95%的 DAA 初治患者清除 HCV。对于先前 DAA 失败的患者，使用补救 SOF/VEL/VOX 方案，病毒治愈率通常超过 95%。
