New hepatitis C virus (HCV) drugs and the hope for a cure: concepts in anti-HCV drug development.
The development of new models and tools has led to the discovery and clinical development of a large number of new anti-hepatitis C virus (HCV) drugs, including direct-acting antivirals and host-targeted agents. Surprisingly, curing HCV infection appears to be easy with these new drugs, provided that a potent drug combination with a high barrier to resistance is used. HCV infection cure rates can be optimized by combining drugs with synergistic antiviral effects, tailoring treatment duration to the patients' needs, and/or using ribavirin. Two HCV drugs have been approved in 2011--telaprevir and boceprevir, both first-wave, first-generation NS3-4A protease inhibitors, two others in 2013/2014--simeprevir, a second-wave, first-generation NS3-4A protease inhibitor, and sofosbuvir, a nucleotide analogue inhibitor of the viral polymerase. Numerous other drugs have reached phase II or III clinical development. From 2015 and onwards, interferon-containing regimens will disappear, replaced by interferon-free regimens yielding infection cure rates over 90%. These therapies will raise new issues, including the need for broad-scale screening and access to care.
National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
Jean-Michel
JM
Pawlotsky
D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D055808:Drug Discovery; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D058990:Molecular Targeted Therapy; D016896:Treatment Outcome
D000998:Antiviral Agents