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DDW 2013: Viral Breakthrough May Occur during Interferon/Ribavirin 'Tail' of HCV Triple Therapy


HCV viral breakthrough is an ongoing possibility during the pegylated interferon/ribavirin continuation phase after triple therapy with telaprevir (Incivek or Incivek or Incivo), especially for difficult-to-treat patients, researchers reported this week at the Digestive Disease Week conference (DDW 2013) in Orlando.

Adding the first-generation HCV protease inhibitors boceprevir (Victrelis) or telaprevir (Incivek or Incivo) to pegylated interferon and ribavirin increases the likelihood of a cure, but treatment remains challenging for some patient populations.

Kali Zhou from the University of California at Los Angeles and colleagues performed a retrospective analysis of viral breakthrough occurring while on treatment among people taking boceprevir or telaprevir triple therapy.

The standard boceprevir regimen involves a 4-week pegylated interferon/ribavirin lead-in, followed by triple therapy for 24 or 32 weeks. Prior relapsers or partial responders without good early response continue on a pegylated interferon/ribavirin "tail" for an additional 12 weeks. Prior null responders and people cirrhosis stay on triple therapy for 44 weeks. The standard telaprevir regimen is 12 weeks of triple therapy, followed by pegylated interferon/ribavirin alone for treatment-naive patients with good early response, or 36 weeks for slow responders, treatment-experienced people, and those with cirrhosis.

The present analysis included 55 chronic hepatitis C patients who received boceprevir or telaprevir triple therapy at UCLA's Pfleger Liver Institute between June 2011 and July 2012.


  • 9 study patients (16%) experienced viral breakthrough while on treatment.
  • All these patients were on telaprevir; there were no breakthroughs on boceprevir.
  • 8 of the 9 experienced breakthrough during the pegylated interferon/ribavirincontinuation phase after triple therapy.
  • The mean time to breakthrough was 21 weeks.
  • 6 patients (67%) who experienced viral breakthrough had harder-to-treat HCV subtype 1a, while 3 (33%) had 1b.
  • 6 of the 9 patients (67%) had advanced fibrosis or cirrhosis (stage F3-F4) according to liver biopsies.
  • 6 breakthrough patients were prior null responders, 1 was a prior relapser, and 2 were treatment-naive.
  • 6 breakthrough patients had ribavirin dose reductions prior to treatment failure, including 2 who also lowered their interferon doses.
  • 6 of the 8 breakthrough patients who underwent resistance testing had telaprevir resistance mutations, all of whom also had cross-resistance to boceprevir.
  • The 6 individuals with resistance all had subtype 1a, while the remaining 2 had 1b.

"Similar to findings in clinical trials, viral breakthrough with DAA for treatment of chronic HCV infection is associated with genotype 1a, advanced liver fibrosis, and prior null treatment response," the researchers concluded.

"In our study, however, a significant proportion of patients experienced viral breakthrough after completion of the DAA portion of triple therapy," they continued. "More frequent virologic assessments during the [pegylated interferon/ribavirin] treatment phase may be useful in a subset of 'higher-risk' patients to expedite compliance with stopping rules and decrease unnecessary treatment burden."



K Zhou, J Ferguson, S Bau, and S Saab.Characteristics of Viral Breakthrough With Direct Acting Agents for Chronic Hepatitis C Treatment in Clinical Practice. Digestive Disease Week. Orlando, May 18-21, 2013. Abstract Sa1040.