Viral Hepatitis Clinical Research Program, The Kirby Institute, The University of New South Wales, Australia.
Curr Opin HIV AIDS. 2011 Nov;6(6):508-13. doi: 10.1097/COH.0b013e32834b87f8.
The landscape of hepatitis C virus (HCV) therapy will change considerably over the next decade with the probable licensure of many HCV direct-acting antiviral (DAA) therapy agents. This review will outline the data on the initial two DAA agents licensed (protease inhibitors telaprevir and boceprevir) and cover potential future therapeutic strategies and challenges for DAA-based therapy, including in the context of HIV/HCV coinfection.
Phase III trials evaluating the addition of telaprevir or boceprevir to pegylated interferon and ribavirin in both HCV treatment naïve and experienced populations with chronic HCV genotype 1 have demonstrated considerable improvements in sustained virological response, with many patients able to shorten total treatment duration from 48 to 24-36 weeks. Although these initial DAA-based treatment results are encouraging, additional toxicity, problematic dosing schedules, and potential drug-drug interactions pose challenges for clinical management, particularly in HIV/HCV coinfection. Phase II trials with telaprevir and boceprevir in HIV/HCV populations are underway. Subsequent DAA agents appear to have improved tolerability and dosing schedules and open the door for interferon (IFN)-free DAA-based combination therapy.
Development of DAA therapy will lead to a major shift in HCV clinical management, particularly with the potential for IFN-free combination therapy.
在未来十年内，丙型肝炎病毒（HCV）治疗领域将发生重大变化，许多 HCV 直接作用抗病毒（DAA）治疗药物可能获得批准。这篇综述概述了首批获得批准的两种 DAA 药物（蛋白酶抑制剂特拉匹韦和博赛匹韦）的数据，并讨论了基于 DAA 的治疗的潜在未来治疗策略和挑战，包括在 HIV/HCV 合并感染的情况下。
在 HCV 治疗初治和慢性 HCV 基因 1 型经验丰富的患者中，评估将特拉匹韦或博赛匹韦添加到聚乙二醇干扰素和利巴韦林中的 III 期试验显示，持续病毒学应答有了显著改善，许多患者能够将总治疗时间从 48 周缩短至 24-36 周。尽管这些基于初始 DAA 的治疗结果令人鼓舞，但额外的毒性、有问题的给药方案和潜在的药物相互作用对临床管理提出了挑战，尤其是在 HIV/HCV 合并感染的情况下。正在进行 HIV/HCV 人群中特拉匹韦和博赛匹韦的 II 期试验。随后的 DAA 药物似乎具有更好的耐受性和给药方案，并为无干扰素（IFN）的 DAA 联合治疗打开了大门。
DAA 治疗的发展将导致 HCV 临床管理的重大转变，特别是可能实现无干扰素的联合治疗。
