Analysis of boceprevir resistance associated amino acid variants (RAVs) in two phase 3 boceprevir clinical studies

Richard J.O. Barnard, John A. Howe, Robert A. Ogert, Stefan Zeuzem, Fred Poordad, Stuart C. Gordon, Robert Ralston, Xiao Tong, Vilma Sniukiene, Julie Strizki, Desmond Ryan, Jianmin Long, Ping Qiu, Clifford A. Brass, Janice Albrecht, Margaret Burroughs, Scott Vuocolo, Daria J. Hazuda

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Background: We investigated the frequency of RAVs among patients failing to achieve SVR in two clinical trials. We also investigated the impact of interferon responsiveness on RAVs and specific baseline RAVs relationship with boceprevir treatment failure. Methods: Data are from 1020 patients enrolled into either SPRINT-2 or RESPOND-2; patients received a 4-week PR lead-in prior to receiving boceprevir or placebo. RAVs were analyzed via population-based sequence analysis of the NS3 protease gene (success rate of >90% at a virus level of ≥10,000. IU/mL). Results: The high SVR rate in patients who received boceprevir resulted in a low rate of RAVs; 7% was detected at baseline in all patients, which rose to 15% after treatment. However, RAVs were detected in 53% of patients that failed to achieve SVR, which declined to 22.8% 6-14 months following cessation of boceprevir therapy. Baseline RAVs alone were not predictive of virologic outcome; poor interferon responsiveness was highly predictive of non-SVR. RAVs were more frequently detected in poor interferon responders. Conclusions: We detected no association between the presence of baseline amino acid variants at boceprevir resistance-associated loci and outcome in the context of good IFN response.

Original languageEnglish (US)
Pages (from-to)329-336
Number of pages8
JournalVirology
Volume444
Issue number1-2
DOIs
StatePublished - Sep 2013

Keywords

  • Boceprevir
  • HCV
  • RAV
  • Resistance
  • Variants

ASJC Scopus subject areas

  • Virology

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