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The effect of the first-generation HCV-protease inhibitors boceprevir and telaprevir and the relation to baseline NS3 resistance mutations in genotype 1: experience from a small Swedish cohort
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
Uppsala Univ Hosp, Dept Med Sci, Sect Infect Dis, Uppsala, Sweden.
Uppsala Univ Hosp, Dept Med Sci, Sect Infect Dis, Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
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2018 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 50-56Article in journal (Refereed) Published
Abstract [en]

Background: The clinical experience with protease-inhibitor (PI) triple regimen appears disappointing regarding effect, side effects, high work load, and costs. This real-world study evaluates baseline and emerging resistance-associated substitutions (RASs) and their significance for treatment outcome.

Method: Thirty-six genotype 1a/b patients treated according to Swedish recommendations during 2011-2013 with triple therapy including pegylated interferon and ribavirin in combination with a protease-inhibitor, either boceprevir (BOC) or telaprevir (TVR), were retrospectively evaluated. Frozen serum samples from the patients were tested for resistance with pan-genotypic population sequencing.

Results: Overall, 56% (20/36) of the patients achieved sustained viral response (SVR). The SVR was comparable between BOC (64%; 9/14) and TVR (50%; 11/22) (p = 0.07), and the IL28B type non-CC (48%; 12/25) and CC (46%; 6/13) (p = 0.77). The SVR was higher in patients without cirrhosis (89.5%; 17/19) (p < 0.0005), in treatment-naive patients (70%; 14/20) (p = 0.02), and those with low viral load (<800,000 IU/mL) (66.7%; 8/12) (p < 0.0002), compared to those with cirrhosis (17.6%; 3/17), treatment-experienced (37.5%; 6/16), and high viral load (>800,000 IU/mL) (50%; 12/24).

Conclusion: PI triple regimes were highly effective in treatment-naive patients without cirrhosis, but in this real-world cohort an inferior effect was evident in cirrhotic and treatment-experienced patients. Although tested on a limited sample, the baseline resistance testing seems to have no impact on prediction of therapy outcome. The reason could be that the baseline RASs T54S and V55A have relatively low resistance towards BOC and TVR. Emerging RASs, mainly R155K, with known high resistance to BOC and TVR were frequently found in non-responders.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD , 2018. Vol. 123, no 1, p. 50-56
Keywords [en]
Boceprevir, hepatitis C, protease inhibitor, RAS, resistance association substitution, telaprevir
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:uu:diva-354543DOI: 10.1080/03009734.2018.1441928ISI: 000428060300006PubMedID: 29536805OAI: oai:DiVA.org:uu-354543DiVA, id: diva2:1233975
Funder
Erik, Karin och Gösta Selanders FoundationAvailable from: 2018-07-20 Created: 2018-07-20 Last updated: 2018-07-20Bibliographically approved

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Kjellin, MidoriLennerstrand, JohanLannergård, Anders

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