Linkage of resistance-associated substitutions in GT1 sofosbuvir + NS5A inhibitor failures treated with glecaprevir/pibrentasvir

Gary P Wang,Gretja L Schnell,Jens J Kort,Gurjit S Sidhu,Layla Schuster,Rakesh L Tripathi,Lois Larsen,Larry C Michael,Ken Bergquist, Ashley Magee, Chandni B Patel,Joan A Whitlock,Ryan Tamashiro,Joy A Peter,Michael W Fried,David R Nelson

Journal of Hepatology（2021）

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摘要

•Primer-ID NGS tracked multiply linked NS5A RASs in GT1 failures re-treated with G/P.•Decreasing SVR12 rates with double- or triple-linked NS5A RASs.•No single GT1a NS5A RAS or NS3 RAS was associated with a reduced SVR12.•Among 13 failures, 4 had treatment-emergent NS3 RASs; 10 had additional NS5A RASs.•85% of GT1a with double- or triple-linked NS5A RASs achieved SVR12 with 16 weeks G/P.

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关键词

Glecaprevir/Pibrentasvir,Hepatitis C therapy,Multiple-linked substitutions,Next-generation sequencing,NS5A resistance,Persistence of treatment-emergent substitutions,Resistance-associated substitutions,Treatment-emergent RASs,Treatment failure

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