Hepatitis C triple therapy with boceprevir and telaprevir

Infection with chronic hepatitis C (HCV) Genotype 1 is a therapeutic challenge due to long duration of therapy, many side-effects and relatively low virologic response rates. With the previous standard of care consisting of pegylated interferon alfa (PEG-IFN) and ribavirin, sustained virologic response rates (SVR) between 40% and 50% were achieved. The current approval of two directly acting inhibitors of the NS3/4A serine protease, boceprevir and telaprevir, in combination with PEG-IFN and ribavirin has changed therapeutic options in HCV Genotype 1. The pivotal Phase 3 clinical trials showed a significant improvement of tripletherapies for both treatment-naïve (SVR 63 - 75%) and previously treated patients (SVR 59 - 65%) compared to the PEG-IFN/ribavirin control arm (SVR 38 - 44% and 17 - 21%, respectively). Beside this considerable progress especially previous null responders showed relatively poor response rates and questions remain concerning the use of the new protease-inhibitors in patients with advanced cirrhosis, HIV-coinfection or patients after liver transplantation. In addition triple-therapy with boceprevir and telaprevir follow complex treatment schedules, serious drug-drug-interactions can be caused and supplemental side effects like an aggravation of anemia (boceprevir, telaprevir) or a rash (telaprevir) have to be expected. There are a number of directly acting antivirals targeting different steps of the HCV replication cycle in clinical development which will expand the range and efficiency of HCV-therapy in the upcoming years. © 2012 Dustri-Verlag Dr. Karl Feistle.