Development of rare resistance-associated variants that are extremely tolerant against NS5A inhibitors during daclatasvir/asunaprevir therapy by a two-hit mechanism

Hepatology Research : the Official Journal of the Japan Society of Hepatology
Yoshihito UchidaSatoshi Mochida

Abstract

The virologic characteristics of resistance-associated variants (RAVs) developing in patients receiving dual oral therapy with daclatasvir/asunaprevir, including those with previous triple therapy with simeprevir, were evaluated. A total of 206 patients with genotype-1b HCV infection, including 5 patients with previous simeprevir therapy, were treated with daclatasvir/asunaprevir for 24 weeks. Resistance-associated variants in the NS5A regions at baseline and during/after therapy were evaluated using cycling-probe real-time polymerase chain reaction combined with direct sequencing. The dynamics of rare RAVs were also assessed using ultra-deep sequencing. A sustained virologic response (SVR12) was achieved in 180 patients (87%); the rates were 95% in patients without baseline NS5A-RAVs and 83%, 59%, and 77% in those with hepatitis C virus (HCV) strains carrying NS5A-L31M, NS5A-Y93H/C, and NS5A-R30Q/H/L mutations, respectively. A multivariate analysis revealed baseline NS5A-R30Q/H/L mutation and NS5A-Y93H mutations as significant factors associated with SVR12. Virologic failure developed in all 5 patients with previous simeprevir treatment, and rare RAVs (HCV strains with NS5A-R30H, NS5A-A92K, NS5A-P29del, and NS5A-P32del) develo...Continue Reading

References

Jun 30, 2010·Antimicrobial Agents and Chemotherapy·Robert A FridellMin Gao
Jun 5, 2012·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Fumitaka SuzukiHiromitsu Kumada
Mar 8, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hiromitsu KumadaEric Hughes
Oct 14, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yohei FujiiSatoshi Mochida
Aug 8, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yohei FujiiSatoshi Mochida

❮ Previous
Next ❯

Citations

Dec 22, 2016·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Masaki HondaYukihiro Inomata
Oct 12, 2018·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Norio ItokawaKatsuhiko Iwakiri
Jul 2, 2019·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Goki SudaNaoya Sakamoto
Dec 18, 2019·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Seiichi MawatariAkio Ido
Dec 15, 2019·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Shohei TsujiSatoshi Mochida
Jul 20, 2017·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Goki SudaUNKNOWN NORTE Study Group
Mar 30, 2019·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Yoshihito UchidaSatoshi Mochida

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2022 Meta ULC. All rights reserved