Treatment failure with new hepatitis C drugs

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Abstract
The combination of pegylated interferon-α plus ribavirin (pegIFNα-RBV) has been the only therapeutic option for patients with chronic hepatitis C virus (HCV) infection during the last decade. Unfortunately, it provides cure to less than a half of individuals infected with HCV genotype 1, which is by far the most prevalent worldwide. The recent introduction of new direct-acting antivirals (DAA) has revolutionized the hepatitis C field. The addition of any of the two recently approved HCV protease inhibitors, boceprevir or telaprevir, to pegIFNα-RBV results in the cure for two-thirds of HCV genotype 1, interferon-naive patients. This paper reviews new antivirals for hepatitis C and HCV treatment failures, along with HCV drug resistance and rescue therapies. The application of early stopping rules may reduce the enrichment of drug-resistant viruses in patients failing first-generation HCV protease inhibitors, potentially allowing more chances of response to rescue interventions with other compounds within the same class in the near future. On the other hand, the advent of DAA belonging to distinct drug families may provide further opportunities for clearing definitively HCV in patients currently failing first-generation HCV protease inhibitors. Thus, hepatitis C has entered a new era that hopefully will end with its eradication. In the meantime, a wise use of DAA is warranted, including adequate selection of candidates for therapy, close monitoring of drug adherence, proper management of side effects and early application of stopping rules.