Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in HCV/HIV Coinfected Patients

Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in HCV/HIV... Background and Aims The prevalence of naturally occurring HCV-NS5A resistance-associated substitutions (RAS) to DAA drugs might affect the response to treatment in HCV/HIV coinfected subjects. There are limited data on the frequency of HCV-NS5A naturally occurring drug-RAS at baseline in HCV/HIV coinfected patients when ultra-deep sequencing meth- odologies are applied. Methods HCV-NS5A-RAS were evaluated among 25 subjects in each group. Patients were matched by age, gender, and hepatic fibrosis stage category to control for selection bias. Results Within subtype 1a, RAS were observed in 28% of HCV monoinfected and 48% of HCV/HIV coinfected subjects. More patients in the HCV/HIV coinfected group had clinically relevant mutations to DAA directed at NS5A. Conclusion While the clinical significance of this observation may be limited in highly drug adherent populations, some HCV/HIV coinfected persons may be at greater risk of viral resistance if suboptimal dosing occurs. Keywords HCV/HIV coinfection · NS5A drug resistance-associated variants/polymorphism · Directly acting antiviral therapy Introduction regimen as demonstrated in the COSMOS study [4, 5]. Simi- larly, preexistence of NS5A M28, Q30, L31, or Y93 can Direct-acting antiviral agents (DAAs) for the treatment of reduce the 12-week sustained viral response (SVR12) to hepatitis C virus (HCV) infection occur in multiple classes http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Digestive Diseases and Sciences Springer Journals

Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in HCV/HIV Coinfected Patients

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Medicine & Public Health; Gastroenterology; Hepatology; Oncology; Transplant Surgery; Biochemistry, general
ISSN
0163-2116
eISSN
1573-2568
D.O.I.
10.1007/s10620-017-4895-1
Publisher site
See Article on Publisher Site

Abstract

Background and Aims The prevalence of naturally occurring HCV-NS5A resistance-associated substitutions (RAS) to DAA drugs might affect the response to treatment in HCV/HIV coinfected subjects. There are limited data on the frequency of HCV-NS5A naturally occurring drug-RAS at baseline in HCV/HIV coinfected patients when ultra-deep sequencing meth- odologies are applied. Methods HCV-NS5A-RAS were evaluated among 25 subjects in each group. Patients were matched by age, gender, and hepatic fibrosis stage category to control for selection bias. Results Within subtype 1a, RAS were observed in 28% of HCV monoinfected and 48% of HCV/HIV coinfected subjects. More patients in the HCV/HIV coinfected group had clinically relevant mutations to DAA directed at NS5A. Conclusion While the clinical significance of this observation may be limited in highly drug adherent populations, some HCV/HIV coinfected persons may be at greater risk of viral resistance if suboptimal dosing occurs. Keywords HCV/HIV coinfection · NS5A drug resistance-associated variants/polymorphism · Directly acting antiviral therapy Introduction regimen as demonstrated in the COSMOS study [4, 5]. Simi- larly, preexistence of NS5A M28, Q30, L31, or Y93 can Direct-acting antiviral agents (DAAs) for the treatment of reduce the 12-week sustained viral response (SVR12) to hepatitis C virus (HCV) infection occur in multiple classes

Journal

Digestive Diseases and SciencesSpringer Journals

Published: Jan 12, 2018

References

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