Telaprevir alone or with peginterferon and ribavirin reduces HCV RNA in patients with chronic genotype 2 but not genotype 3 infections.

Abstract

BACKGROUND & AIMS:

We evaluated antiviral activity of 2 weeks therapy with telaprevir alone, peginterferon alfa-2a and ribavirin (PR), or all 3 drugs (TPR) in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype 2 or 3 infections.

METHODS:

We performed a randomized, multicenter, partially blinded study of patients (23 with HCV genotype 2, 26 with genotype 3) who received telaprevir (750 mg every 8 h), placebo plus PR (peginterferon, 180 μg, once weekly and ribavirin, 400 mg, twice daily), or TPR for 15 days, followed by PR for 22 or 24 weeks. Plasma levels of HCV RNA were quantified.

RESULTS:

Levels of HCV RNA decreased in all patients with HCV genotype 2, including those who received telaprevir monotherapy. The decrease was more rapid among patients who received telaprevir. By day 15, 0% (telaprevir), 40% (TPR), and 22% (PR) of patients with HCV genotype 2 had undetectable levels of HCV RNA; rates of sustained virologic response were 56%, 100%, and 89%, respectively. Overall, 6 of 9 HCV genotype 2 patients that received only telaprevir had viral breakthrough within 15 days after an initial response. HCV RNA levels decreased slightly among patients with HCV genotype 3 who received telaprevir and decreased rapidly among patients given PR or TPR (telaprevir had no synergistic effects with PR). Sustained virologic response rates were 50%, 67%, and 44% among patients given telaprevir, TPR, or PR respectively; 7 patients with HCV genotype 3 relapsed after therapy (2 given telaprevir, 3 given TPR, and 2 given PR) and 3 patients with HCV genotype 3 had viral breakthrough during telaprevir monotherapy. The incidence of adverse events was similar among groups.

CONCLUSIONS:

Telaprevir monotherapy for 2 weeks reduces levels of HCV RNA in patients with chronic HCV genotype 2 infections, but has limited activity in patients with HCV genotype 3.

• Authors: Graham R Foster, Christophe Hézode, Jean-Pierre Bronowicki, Giampiero Carosi, Ola Weiland, Lieselotte Verlinden, Rolf van Heeswijk, Ben van Baelen, Gaston Picchio, Maria Beumont
• Journal: Gastroenterology (Gastroenterology) Vol. 141 Issue 3 Pg. 881-889.e1 (Sep 2011) ISSN: 1528-0012 [Electronic] United States
• PMID: 21699786 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antiviral Agents
• Interferon-alpha
• Oligopeptides
• RNA, Viral
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• telaprevir
• peginterferon alfa-2a

Topics

• Adult
• Antiviral Agents (adverse effects, pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (drug therapy, genetics, metabolism)
• Humans
• Interferon-alpha (adverse effects, pharmacology, therapeutic use)
• Male
• Middle Aged
• Oligopeptides (adverse effects, pharmacology, therapeutic use)
• Polyethylene Glycols (adverse effects, pharmacology, therapeutic use)
• RNA, Viral (blood, drug effects, genetics)
• Recombinant Proteins (adverse effects, pharmacology, therapeutic use)
• Ribavirin (adverse effects, pharmacology, therapeutic use)
• Single-Blind Method
• Treatment Outcome