Current and emerging antiviral treatments for hepatitis C infection

Abstract

Newly licensed direct acting antivirals for hepatitis C virus HCV are able to cure up to 75% of patients chronically infected with genotype-1 infection, which is the predominant HCV strain in Europe and North America. Emerging antiviral therapies promise further increases in virological response, as well as improved tolerability, reduced duration of therapy, and will potentially eliminate the need for interferon use. This review highlights the main therapeutic agents used in current standard of care, including telaprevir and boceprevir. It goes on to evaluate the mechanisms of emerging drugs, their stage of development and response rates seen in research to date. Finally, it projects into the not too distant future to consider treatment strategies involving combinations of agents and interferon-free therapies, and in which patients they might prove most successful.

Figure 1

HCV viral life cycle and therapeutic targets for new drug classes (A) HCV virus binding and entry via receptor-mediated endocytosis (targeted by entry inhibitors); (B) RNA release into the cytoplasm; (C) Translation into a polypeptide on the ribosome, and processing into viral proteins that form structural components of the virus (targeted by protease inhibitors); (D) RNA replication in the endoplasmic reticulum (targeted by protease, polymerase, NS5A and cyclophilin inhibitors, and antagomirs); (E) RNA packaging and assembly (targeted by NS5A inhibitors); and (F) virion maturation and release (targeted by glycosylation inhibitors). (Figure reproduced with permission from Nature Publishing Group, Moradpour et al. 2007 [31], copyright)