Digestive Diseases and Sciences

, Volume 63, Issue 3, pp 645–652 | Cite as

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

  • Enass A. Abdel-hameed
  • Susan D. Rouster
  • Ceejay L. Boyce
  • Xiang Zhang
  • Jacek Biesiada
  • Mario Medvedovic
  • Kenneth E. Sherman
Original Article
First Online:
Received:
Accepted:

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 methodologies 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 
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Notes

Acknowledgements

This research was supported by Merck Investigator Studies Program (MISP) to K.E.S. and support to the Center for Environmental Genetics, NIEHS P30-ES006096.

Compliance with ethical standards

Conflicts of interest

K.E.S. has received research support (to institution) from AbbVie, BMS, Gilead, Merck, MedImmune, Innovio. K.E.S. has served as a consultant to Gilead, Merck, MedImmune, and Abbott Labs. The authors E.A.A., S.D.R., C.L.B., X.Z., J.C., J.B., and M.M. have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of Cincinnati College of MedicineCincinnatiUSA
  2. 2.Department of Environmental HealthUniversity of CincinnatiCincinnatiUSA

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