Resistance mechanisms in HCV: from evolution to intervention

Abstract

Recent advances in our understanding of the HCV life cycle and the functions of virally encoded proteins enabled the development of specifically targeted antiviral therapies for HCV, which directly inhibit HCV replication. Early clinical trials show great efficacy; however, from the first trials it became evident that, similar to HIV and HBV, selection of resistant variants will be problematic. Error-prone replication of HCV, resulting in a complex quasispecies population within each infected individual, enables rapid adaptation to changing environments. In this review, the evolutionary mechanisms involved in the selection process resulting in drug resistance are discussed. We give an overview of the resistance profiles to recently developed HCV protease and polymerase inhibitors and discuss potential implications for future treatment developments.

Keywords::

• hepatitis C virus
• polymerase inhibitor
• protease inhibitor
• quasispecies
• resistance mutation
• selection pressure
• viral fitness

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.