Department of Medicine, Division of Infectious Diseases, University of Ottawa, Canada.
Clin Infect Dis. 2012 Aug;55(3):418-25. doi: 10.1093/cid/cis375. Epub 2012 Apr 4.
Development of more effective hepatitis C (HCV) antivirals has been rapid. The addition of orally administered medications that target the virus (direct acting antivirals [DAA]) to pegylated interferon and ribavirin have dramatically increased sustained virologic response rates in genotype 1-infected patients. However, the side effect profile remains challenging and the dosing schedule complicated. The DAAs currently in development possess the promise of once- or twice-daily dosing schedules, improved tolerance profiles, higher resistance barriers, and pan-genotypic antiviral activity. Emerging interferon-sparing, combination DAA data demonstrates that an interferon is not essential to achieve sustained virological response. This will expand the proportion of HCV-infected patients who can be considered for therapy and will allow for better-tolerated regimens. Expertise in HCV antiviral resistance, drug metabolism, and drug-drug interactions and optimization of drug adherence are now key requirements in the DAA era.
丙型肝炎(HCV)抗病毒药物的研发进展迅速。在聚乙二醇干扰素和利巴韦林的基础上,增加了针对病毒的口服药物(直接作用抗病毒药物[DAA]),显著提高了基因型 1 感染患者的持续病毒学应答率。然而,其副作用谱仍然具有挑战性,用药方案也很复杂。目前正在开发的 DAA 有望实现每日一次或两次的给药方案,改善耐受谱,提高耐药屏障,并具有泛基因型抗病毒活性。新兴的无干扰素、联合 DAA 数据表明,干扰素并非实现持续病毒学应答所必需的。这将扩大可以考虑进行治疗的 HCV 感染患者的比例,并允许使用耐受性更好的方案。在 DAA 时代,HCV 抗病毒耐药性、药物代谢和药物相互作用方面的专业知识以及药物依从性的优化是关键要求。