The advent of protease inhibitors for treating HCV: General considerations

Fred Poordad, Vandana Khungar

Research output: Contribution to journalReview articlepeer-review


The protease enzyme of the hepatitis C virus (HCV) has been the first major target for the development of direct acting antivirals (DAAs). Boceprevir (BOC) and telaprevir (TVR) are the first two protease inhibitors approved by the FDA that achieve 70%-80% viral eradication rates in treatment naïve genotype 1 HCV patients. Since the early phase studies, the BOC regimen showed moderate viral load decline in genotype 1 patients. The phase 2 clinical trial in treatment naïve patients (SPRINT-1) demonstrated that a lead-in period with pegylated interferon-α2b (PEG-IFN-α2b) and ribavirin (RBV) provided interferon responsiveness predictability. The SPRINT-2 and RESPOND-2 phase 2 trials assessed the efficacy and tolerability of BOC plus PEG-IFN-α2b and RBV treatment in previously untreated patients and in partial interferon responders or relapsers, respectively. The PROVE 1 and 2 studies were the early phase trials that evaluated TVR in treatment naïve patients. Thanks to the phase 2 trial (PROVE 3), it was clear that a long course of treatment with TVR was not feasible. The ADVANCE and the ILLUMINATE trials enrolled previously untreated patients for phase 3 studies evaluating TVR in combination with PEG-IFN-α2b and RBV, while the REALIZE trial investigated efficacy and tolerability of TVR in patients who failed previous treatment with PEG-IFN-α and RBV. Stopping rules, clinical experience with the drugs and future perspectives are also reviewed in this article.

Original languageEnglish (US)
Pages (from-to)7-13
Number of pages7
JournalHot Topics in Viral Hepatitis
Issue number25
StatePublished - 2012
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases


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