Wyles David L, Kaihara Kelly A, Vaida Florin, Schooley Robert T
Department of Medicine, Divivion of Infectious Diseases, University of California-San Diego, 9500 Gilman Drive, MC 0711, La Jolla, CA 92093, USA.
J Virol. 2007 Mar;81(6):3005-8. doi: 10.1128/JVI.02083-06. Epub 2006 Dec 20.
Chronic hepatitis C virus (HCV) infection is a significant worldwide health problem with limited therapeutic options. A number of novel, small molecular inhibitors of HCV replication are now entering early clinical trials in humans. Resistance to small molecular inhibitors is likely to be a significant hurdle to their use in patients. A systematic assessment of combinations of interferon and/or novel anti-hepatitis C virus agents from several different mechanistic classes was performed in vitro. Combinations of inhibitors with different mechanisms of action consistently demonstrated more synergy than did compounds with similar mechanisms of action. These results suggest that combinations of inhibitors with different mechanisms of action should be prioritized for assessment in clinical trials for chronic hepatitis C virus infection.
慢性丙型肝炎病毒(HCV)感染是一个全球性的重大健康问题,治疗选择有限。目前,一些新型的HCV复制小分子抑制剂正进入人体早期临床试验阶段。小分子抑制剂的耐药性可能是其在患者中应用的重大障碍。我们在体外对来自几种不同作用机制类别的干扰素和/或新型抗丙型肝炎病毒药物的组合进行了系统评估。与具有相似作用机制的化合物相比,具有不同作用机制的抑制剂组合始终表现出更强的协同作用。这些结果表明,在慢性丙型肝炎病毒感染的临床试验评估中,应优先考虑具有不同作用机制的抑制剂组合。