کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5826042 | 1558130 | 2014 | 9 صفحه PDF | دانلود رایگان |

- HCV NS3/4A serine protease inhibitors represent a major breakthrough in HCV treatment.
- 15 agents have been licensed (boceprevir, telaprevir, simeprevir) or are in clinical development.
- Second-wave drugs are more tolerable, have easier dosing schedules, wider genotypic activity.
- Genetic barrier to resistance remains low, particularly with viral subtype 1a.
- Combining with polymerase inhibitors and/or NS5A-inhibitors without interferon allows >90% cure rates after short treatments.
HCV NS3/4A serine protease inhibitors are the first class of direct acting antivirals (DAA) introduced in clinical practice. The first generation agents, selective against HCV genotype 1, are used in association with pegylated interferons and ribavirin allowing increased cure rates at the price of increased toxicity, significant drug interactions and high risk of selecting mutants conferring cross-resistance to the entire class. A large number of second-wave HCV protease inhibitors are currently in clinical development. Advancements include higher potency, activity against a wider number of genotypes, improved tolerability, easier dosing schedules, although their genetic barrier to resistance remains low, especially for subtype 1a, except for the most recent grazoprevir and ACH-2684. The most relevant progress regards the combination with other classes of DAA allowing construction of interferon-free regimens of short duration, good tolerability with exceptionally high cure rates.
Journal: Current Opinion in Pharmacology - Volume 18, October 2014, Pages 9-17