Division of Clinical Microbiology, F68, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Sweden.
Drug Resist Updat. 2013 Jul-Nov;16(3-5):60-7. doi: 10.1016/j.drup.2013.06.001. Epub 2013 Aug 2.
Presently the development of new therapies for hepatitis C virus (HCV) is rapidly moving forward. Almost every week new data appear on how direct acting antivirals (DAAs) succeed or fail in clinical trials. Despite the potency of many of the DAA combinations, the effect exerted by ribavirin (RBV) is still needed for an effective therapy in many new DAA combinations. Due to the strong antiviral effect of DAAs, it is likely that a major complementary therapeutic effect exerted by RBV is immune modulation resulting in an increased barrier to development of resistance. For HCV genotype 1a infections elimination of pegylated interferon, is not possible in many DAA combinations without jeopardizing the results. The host immune response is thus likely to play a key role even during DAA-based therapies. Hence, T cells may recognize and eliminate viral variants with resistance to the DAAs. We herein show several examples where this may be the case, supporting the rationale of including the host response also in the new therapeutic regimens. This review will describe the potential benefits of combining various DAAs with means to activate the specific immune response against HCV.
目前，丙型肝炎病毒 (HCV) 的新疗法的发展正在迅速推进。几乎每周都有新的数据显示直接作用抗病毒药物 (DAA) 在临床试验中的成功或失败。尽管许多 DAA 联合用药的疗效很强，但在许多新的 DAA 联合用药中，仍需要利巴韦林 (RBV) 发挥其有效的治疗作用。由于 DAA 的强大抗病毒作用，利巴韦林可能通过免疫调节发挥主要的互补治疗作用，从而增加了产生耐药性的障碍。对于 HCV 基因型 1a 感染，在许多 DAA 联合用药中，如果不危及治疗结果，无法消除聚乙二醇干扰素。因此，宿主免疫反应可能在 DAA 治疗期间发挥关键作用。因此，T 细胞可能会识别和消除对 DAA 具有耐药性的病毒变异体。本文介绍了几种可能的情况，支持了在新的治疗方案中也包括宿主反应的合理性。这篇综述将描述联合使用各种 DAA 与激活针对 HCV 的特异性免疫反应的方法的潜在益处。
