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

Authors: Abdel-Hameed, Enass A; Rouster, Susan D; Boyce, Ceejay L; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Sherman, Kenneth E

Published In Dig Dis Sci, (2018 03)

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.

PubMed ID: 29330726

MeSH Terms: Adult; Antiviral Agents; Benzofurans; Case-Control Studies; Coinfection/virology*; Drug Combinations; Drug Resistance, Viral/genetics*; Female; HIV Infections/virology*; Hepacivirus/genetics*; Hepatitis C/drug therapy; Hepatitis C/virology*; High-Throughput Nucleotide Sequencing; Humans; Imidazoles; Male; Middle Aged; Quinoxalines; Viral Nonstructural Proteins/genetics*