Journal article
Hepatitis C Virus Variants with Decreased Sensitivity to Direct-Acting Antivirals (DAAs) Were Rarely Observed in DAA-Naive Patients prior to Treatment
Journal of virology, Vol.87(3), pp.1544-1553
02/01/2013
DOI: 10.1128/JVI.02294-12
PMCID: PMC3554180
PMID: 23152524
Abstract
The prevalence of naturally occurring hepatitis C virus (HCV) variants that are less sensitive to direct-acting antiviral (DAA) inhibitors has not been fully characterized. We used population sequence analysis to assess the frequency of such variants in plasma samples from 3,447 DAA-naive patients with genotype 1 HCV. In general, HCV variants with lower-level resistance (3- to 25-fold increased 50% inhibitor concentration [IC
50
]) to telaprevir were observed as the dominant species in 0 to 3% of patients, depending on the specific variant, whereas higher-level resistant variants (>25-fold-increased IC
50
) were not observed. Specific variants resistant to NS5A inhibitors were predominant in up to 6% of patients. Most variants resistant to nucleo(s/t)ide active-site NS5B polymerase inhibitors were not observed, whereas variants resistant to non-nucleoside allosteric inhibitors were observed in up to 18% of patients. The presence of DAA-resistant variants in NS5A, NS5B, or NS3 (including telaprevir-resistant variants), in baseline samples of treatment-naive patients receiving a telaprevir-based regimen in phase 3 studies did not affect the sustained viral response (SVR). Treatment-naive patients with viral populations containing the telaprevir-resistant variants NS3 V36M, T54S, or R155K at baseline achieved a 74% SVR rate, whereas patients with no resistant variants detected prior to treatment achieved a 76% SVR rate. The effect of specific resistant variant frequency on response to various DAA treatments in different patient populations, including interferon nonresponders, should be further studied.
Details
- Title: Subtitle
- Hepatitis C Virus Variants with Decreased Sensitivity to Direct-Acting Antivirals (DAAs) Were Rarely Observed in DAA-Naive Patients prior to Treatment
- Creators
- Doug J. Bartels - Vertex Pharmaceuticals (United States)James C. Sullivan - Vertex Pharmaceuticals (United States)Eileen Z. Zhang - Vertex Pharmaceuticals (United States)Ann M. Tigges - Vertex Pharmaceuticals (United States)Jennifer L. Dorrian - Vertex Pharmaceuticals (United States)Sandra De Meyer - Janssen (Belgium)Darin Takemoto - Vertex Pharmaceuticals (United States)Elizabeth Dondero - Vertex Pharmaceuticals (United States)Ann D. Kwong - Vertex Pharmaceuticals (United States)Gaston Picchio - Janssen (United States)Tara L. Kieffer - Vertex Pharmaceuticals (United States)
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.87(3), pp.1544-1553
- DOI
- 10.1128/JVI.02294-12
- PMID
- 23152524
- PMCID
- PMC3554180
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 02/01/2013
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984284450902771
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