Hepatitis C Resistance-Associated Substitutions Among People Who Inject Drugs Treated With Direct-Acting Antiviral-Containing Regimens

Matthew J Akiyama; Lindsey Riback; Jacqueline D Reeves; Yolanda S Lie; Linda Agyemang; Brianna L Norton; Julia H Arnsten; Alain H Litwin

doi:10.1093/ofid/ofab474

Hepatitis C Resistance-Associated Substitutions Among People Who Inject Drugs Treated With Direct-Acting Antiviral-Containing Regimens

Open Forum Infect Dis. 2021 Sep 30;8(10):ofab474. doi: 10.1093/ofid/ofab474. eCollection 2021 Oct.

Authors

Matthew J Akiyama¹, Lindsey Riback¹, Jacqueline D Reeves², Yolanda S Lie², Linda Agyemang¹, Brianna L Norton¹, Julia H Arnsten¹, Alain H Litwin^{3

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Affiliations

¹ Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NEW YORK, USA.
² Monogram Biosciences, LabCorp, South San Francisco, California, USA.
³ Prisma Health, Greenville, South Carolina, USA.
⁴ University of South Carolina School of Medicine, Greenville, South Carolina, USA.
⁵ Clemson University, Clemson, South Carolina, USA.

Abstract

Background: Resistance-associated substitutions (RASs) to HCV direct-acting antivirals (DAAs) can contribute to virologic failure and limit retreatment options. People who inject drugs (PWID) are at highest risk for transmission of resistant virus. We report on RASs at baseline and after virologic failure in DAA-naive and protease inhibitor-experienced PWID.

Methods: We sequenced the NS3/4A, NS5A, and NS5B regions from 150 PWID with genotype 1 (GT1) viruses; 128 (85.3%) GT1a, 22 (14.7%) GT1b.

Results: Among the 139 (92.7%) DAA-naive PWID, 85 of 139 (61.2%) had baseline RASs-67 of 139 (48.2%) in NS3 (predominantly Q80K/L); 25 of 139 (18.0%) in NS5A; and 8 of 139 (5.8%) in NS5B. Of the 11 protease inhibitor-experienced participants, 9 had baseline NS3 RASs (V36L N = 1, Q80K N = 9) and 4 had baseline NS5A RASs (M28V N = 2, H58P N = 1, A92T N = 1). Among the 11 participants who had posttreatment samples with detectable virus (7 treatment failures, 1 late relapse, 3 reinfections), 1 sofosbuvir/ledipasvir failure had a baseline H58P. Two sofosbuvir/ledipasvir-treated participants developed new NS5A mutations (Q30H, Y93H, L31M/V). Otherwise, no RASs were detected.

Conclusions: Our results demonstrate RAS prevalence among DAA-naive PWID is comparable to that in the general population. Only 2 of 150 (1.3%) in our longitudinal cohort developed treatment-emergent RASs. Concern for transmission of resistant virus may therefore be minimal.

Keywords: direct-acting antivirals (DAAs); hepatitis C virus (HCV); people who inject drugs (PWID); resistance-associated substitutions (RASs); transmitted resistance.

Abstract

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