Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Immunol Res. 2012 Jun;52(3):200-10. doi: 10.1007/s12026-011-8263-5.
With the approval in 2011 of the protease inhibitors Victrelis and Incivek, direct-acting antivirals have begun to revolutionize HCV treatment. Although the addition of Incivek or Victrelis to PEGylated IFNα and ribavarin (pIFNα/RBV) may improve cure rates and shorten the treatment duration of the "old" standard of care (SOC), this triple therapy will not be suitable for patients intolerant to pIFNα or RBV. The efficacy of this triple therapy will also certainly be attenuated in pIFNα/RBV non-responders. As Incivek is inactive against genotype 3 (GT3) combined with the fact that all protease inhibitors and most of the non-nucleoside polymerase inhibitors in development are active primarily against GT1, pIFNα/RBV will remain the SOC for non-GT1 until new classes of inhibitors enter into clinical practice. GT1 patients who do not respond to this new triple therapy will have developed resistance to protease inhibitors that will limit future treatment options. There is thus an important need for the identification of new potent HCV agents. A novel class of HCV inhibitors that have great potential for the treatment for HCV has recently emerged: the host-targeting antivirals cyclophilin inhibitors.
随着蛋白酶抑制剂 Victrelis 和 Incivek 于 2011 年获得批准，直接作用抗病毒药物开始彻底改变 HCV 的治疗方法。虽然将 Incivek 或 Victrelis 与聚乙二醇干扰素 α 和利巴韦林（pIFNα/RBV）联合使用可能会提高治愈率并缩短“旧”标准治疗（SOC）的治疗持续时间，但这种三联疗法并不适合对 pIFNα 或 RBV 不耐受的患者。这种三联疗法的疗效在 pIFNα/RBV 无应答者中肯定会减弱。由于 Incivek 对基因型 3（GT3）无效，并且开发中的所有蛋白酶抑制剂和大多数非核苷聚合酶抑制剂主要针对 GT1 有效，因此 pIFNα/RBV 将仍然是非 GT1 的 SOC，直到新类别的抑制剂进入临床实践。对这种新三联疗法无应答的 GT1 患者将对蛋白酶抑制剂产生耐药性，这将限制未来的治疗选择。因此，迫切需要鉴定新的有效的 HCV 药物。一类新型 HCV 抑制剂最近出现，具有治疗 HCV 的巨大潜力：宿主靶向抗病毒药物亲环素抑制剂。
