Abstract
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.
Keywords
hepatitis C virus - direct-acting antivirals - host-targeted agents - simeprevir -
sofosbuvir
