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NS5A-P32 deletion as a factor involved in virologic failure in patients receiving glecaprevir and pibrentasvir.

Authors :
Uemura, Hayato
Uchida, Yoshihito
Kouyama, Jun-ichi
Naiki, Kayoko
Tsuji, Shohei
Sugawara, Kayoko
Nakao, Masamitsu
Motoya, Daisuke
Nakayama, Nobuaki
Imai, Yukinori
Tomiya, Tomoaki
Mochida, Satoshi
Source :
Journal of Gastroenterology; May2019, Vol. 54 Issue 5, p459-470, 12p, 1 Diagram, 3 Charts, 3 Graphs
Publication Year :
2019

Abstract

<bold>Background: </bold>This study sought to clarify the factors involved in virologic failure in patients with HCV receiving retreatment with glecaprevir/pibrentasvir (GLE/PIB) in real-world practice.<bold>Methods: </bold>Forty-two patients who had previously received direct-acting antivirals (DAAs) therapies consisting of 35, 3, 3, and 1 patient(s) with genotype (GT)-1b, GT-2a, GT-2b, and GT-3b HCV, respectively, received GLE/PIB for 12 weeks. Resistance-associated substitutions (RASs) at baseline were evaluated, and the dynamics of NS5A-RASs were assessed by deep sequencing in patients showing virologic failure.<bold>Results: </bold>Baseline NS5A-RASs were found in all the patients with GT-1b HCV including 16 patients with NS3-RASs. In contrast, both NS5A-RASs and NS3-RASs were absent in 3 and 2 patients with GT-2a and GT-2b HCV, respectively. Virologic failure occurred in 3 patients with GT-1b HCV with NS5A-P32del, while a sustained virologic response (SVR) was achieved in the remaining 39 patients including those with GT-1b HCV carrying NS5A-L31V + Y93H and NS5A-A92K. Virologic failure even occurred in a patient in whom the NS5A-P32del HCV strains had become undetectable by direct sequencing, and the percentage of such strains relative to the total HCV strains was 10%, as determined by deep sequencing. In the other patient with GT-1b HCV with NS5A-P32del, NS3-A156A/V/S were found at 4 weeks after GLE/PIB therapy, but had disappeared at 11 weeks, as determined by direct sequencing.<bold>Conclusions: </bold>GLE/PIB was effective for patients with HCV who failed to achieve an SVR after prior DAA therapies except in those with GT-1b HCV carrying NS5A-P32del even when such strains became undetectable by direct sequencing. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09441174
Volume :
54
Issue :
5
Database :
Complementary Index
Journal :
Journal of Gastroenterology
Publication Type :
Academic Journal
Accession number :
135927606
Full Text :
https://doi.org/10.1007/s00535-018-01543-9