Grünberger Christian, Wyles David L, Kaihara Kelly A, Schooley Robert T
Department of Medicine, Division of Infectious Diseases, University of California, San Diego, La Jolla, USA.
J Infect Dis. 2008 Jan 1;197(1):42-5. doi: 10.1086/524062.
Small molecular inhibitors of hepatitis C virus (HCV) replication provide remarkable potency, but the rapid selection of resistance mutations will require that these agents be used in combination for clinical treatment. Using a model HCV replicon system, we have extended prior in vitro studies of double combinations of candidate small molecular inhibitors to studies evaluating the simultaneous use of 3 agents. This was done in an effort to anticipate conditions that might ultimately be required clinically. We formally demonstrate synergistic antiviral activity with 3-drug combinations in this model, further supporting the concept of clinical investigations of combination therapy for HCV infection.
丙型肝炎病毒（HCV）复制的小分子抑制剂具有显著的效力，但耐药突变的快速出现意味着这些药物需要联合用于临床治疗。利用一个HCV复制子模型系统，我们将之前对候选小分子抑制剂双重组合的体外研究扩展到了对三种药物同时使用的评估研究。这样做是为了预测临床上最终可能需要的情况。我们在该模型中正式证明了三种药物联合具有协同抗病毒活性，进一步支持了针对HCV感染进行联合治疗临床研究的理念。
