Directly acting antivirals against hepatitis C virus.

The approval of directly acting antivirals (DAA) for the treatment of chronic hepatitis C virus (HCV) infection will represent a major breakthrough for the 180 million persons infected worldwide. Paradoxically, hepatitis C is the only human chronic viral disease that can be cured, as all other pathogenic viruses infecting humans either display self-limited courses or establish non-eradicable persistent infections. Until now, treatment of chronic hepatitis C consisted of the combination of peginterferon-α plus ribavirin, which provided limited rates of cure and was associated with frequent side effects. Several DAA have been identified that inhibit the NS3 protease, the NS5B polymerase or the NS5A replication complex, and have entered the final steps of clinical development. These molecules, coupled with significant progress made in the recognition of more potent and safe interferon forms (e.g. interferon-λ) and host protein targets (e.g. alisporivir), are opening a new era in hepatitis C therapeutics. The expectations are so great that, to some extent, it is reminiscent of what happened in 1996 in the HIV field when the introduction of the first protease inhibitors as part of triple combinations revolutionized antiretroviral therapy. To maximize treatment success and reduce the likelihood of drug resistance selection, a proper individualization of hepatitis C therapy will be required, choosing the most convenient drugs and strategies according to distinct viral and host profiles. The complexity of HCV therapeutics has reached a point that presumably will lead to the birth of a new specialist, the HCV doctor.