期刊
JOURNAL OF CLINICAL VIROLOGY
卷 53, 期 2, 页码 174-177出版社
ELSEVIER
DOI: 10.1016/j.jcv.2011.11.004
关键词
Hepatitis C virus; Antiviral treatment; Direct acting antiviral (DAA); Protease inhibitor; Telaprevir; Sequence analysis; Phylogenetic analysis
类别
资金
- Merck/Schering-Plough
- PRA International
- Roche
- Vertex
- Gilead
- Janssen Cilag
- Boehringer Ingelheim
- Bristol-Myers Squibb
- Vertex Pharmaceuticals Incorporated
Background: Telaprevir is a selective inhibitor of the hepatitis C virus NS3 center dot 4A serine protease. Treatment with telaprevir resulted in a rapid HCV-RNA decline in chronic hepatitis C genotype 1 patients. Objectives: To report the clinical and viral course of a patient treated with telaprevir in combination with pegylated interferon-alpha-2a and ribavirin in a Phase 2 clinical trial (PROVE3). Study design: This previous non-responder to interferon based therapy was treated for 40 weeks with a telaprevir, pegylated interferon alpha-2a, and ribavirin regimen. Viral sequencing and phylogenetic analysis were performed before, during and after therapy. Results: The patient, a 54 years old male patient, experienced a viral relapse 4 weeks post-treatment and HCV-RNA levels continued to increase 14 weeks post-treatment (150,000 IU/mL). The viral population, which was wild type at baseline, consisted of only V36A variants at both of these post-treatment time-points. Subsequently, this patient had a transient disappearance of HCV-RNA for more than 1 year in the absence of antiviral therapy. Thereafter, HCV-RNA reappeared again with a viral population consisting of only wild type virus. Phylogenetic analysis of NS3 center dot 4A corresponded with a viral population bottleneck resulting in changes in viral quasispecies. Conclusion: In this case report, significant viral load reductions resulted in a genetic bottleneck leading to a reduction of variability in the hepatitis C viral population. We hypothesize that the reduction in viral heterogeneity potentially led to a reduced viral capacity to adapt to a host immune response leading to a transient loss of detectable HCV-RNA. (C) 2011 Elsevier B.V. All rights reserved.
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