Gozlan, Yael, Ben-Ari, Ziv, Moscona, Roy ORCID: 0000-0001-6860-4917, Shirazi, Rachel, Rakovsky, Aviya, Kabat, Arij, Veizman, Ella, Berdichevski, Tania, Weiss, Peretz, Cohen-Ezra, Oranit, Lurie, Yoav, Gafanovich, Inna, Braun, Marius, Cohen-Naftaly, Michal, Shlomai, Amir, Shibolet, Oren, Zigmond, Ehud, Zuckerman, Eli, Carmiel-Haggai, Michal, Nimer, Assy, Hazzan, Rawi, Maor, Yaakov, Kitay-Cohen, Yona, Shemer-Avni, Yonat, Kra-Oz, Zipi, Schreiber, Licita, Peleg, Ofer, Sierra, Saleta, Harrigan, P. Richard, Mendelson, Ella and Mor, Orna (2017). HCV genotype-1 subtypes and resistance-associated substitutions in drug-naive and in direct-acting antiviral treatment failure patients. Antivir. Ther., 22 (5). S. 431 - 442. LONDON: INT MEDICAL PRESS LTD. ISSN 1359-6535

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Abstract

Background: Direct-acting antiviral (DAA) treatment regimens and response rates of patients with HCV genotype-1 (GT1) are currently considered subtype-dependent. Identification of clinically relevant resistance-associated substitutions (RASs) in the NS3 and NS5A proteins at baseline and in DAA failures, may also impact clinical decisions. Methods: In a multicentre cohort study (n=308), NS3 or NS5B sequencing (n=248) was used to discriminate between GT1 subtypes. The correlation between baseline NS3 and NS5A RASs on the 12-week sustained virological response (SVR12) rates of 160 of the patients treated with second-generation DAAs was also assessed. Posttreatment resistance analysis was performed on samples from 58 patients exhibiting DAA virological failure. Results: GT1a, GT1b and GT1d subtypes were identified in 23.0%, 75.4% and 1.2% of tested samples. GT1b was most prevalent (97.7%, 128/131) among patients born in the former Soviet Union. The Q80K NS3 RAS was identified in 17.5% (10/57) of the GT1a carriers, most of whom were Israeli-born. NS3 and NS5A baseline RASs showed a negligible correlation with SVR12 rates. Treatment-emergent RASs were observed among 8.9% (4/45) and 76.9% (10/13) of first-and second-generation DAA failures, respectively, with D168V/E (NS3), Y93H and L31M (NS5A) being the most prevalent mutations. Conclusions: NS3 sequencing analysis can successfully discriminate between GT1 subtypes and identify NS3 amino acid substitutions. While pre-treatment NS3 and NS5A RASs marginally affect second-generation DAA SVR12 rates, post-treatment resistance analysis should be considered prior to re-therapy.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gozlan, YaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ben-Ari, ZivUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moscona, RoyUNSPECIFIEDorcid.org/0000-0001-6860-4917UNSPECIFIED
Shirazi, RachelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rakovsky, AviyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kabat, ArijUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Veizman, EllaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berdichevski, TaniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiss, PeretzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cohen-Ezra, OranitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lurie, YoavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gafanovich, InnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braun, MariusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cohen-Naftaly, MichalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shlomai, AmirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shibolet, OrenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zigmond, EhudUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zuckerman, EliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carmiel-Haggai, MichalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nimer, AssyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hazzan, RawiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maor, YaakovUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kitay-Cohen, YonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shemer-Avni, YonatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kra-Oz, ZipiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schreiber, LicitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peleg, OferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sierra, SaletaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harrigan, P. RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mendelson, EllaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mor, OrnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-242939
DOI: 10.3851/IMP3123
Journal or Publication Title: Antivir. Ther.
Volume: 22
Number: 5
Page Range: S. 431 - 442
Date: 2017
Publisher: INT MEDICAL PRESS LTD
Place of Publication: LONDON
ISSN: 1359-6535
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
C VIRUS GENOTYPE; NS3 PROTEASE; INFECTION; REGION; EPIDEMIOLOGY; RECOMBINANT; VARIANTS; THERAPY; 1BMultiple languages
Infectious Diseases; Pharmacology & Pharmacy; VirologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/24293

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