454. Hepatitis C Resistance Associated Variants Among People Who Inject Drugs Treated with Direct-Acting Antiviral-Containing Regimens
Session: Poster Abstract Session: Hepatitis C
Thursday, October 27, 2016
Room: Poster Hall
  • IDSA 2016 HCV RAVs Poster.pdf (531.5 kB)
  • Background: Resistance-associated variants (RAVs) to HCV direct-acting antivirals (DAAs) have been associated with virologic failure and may limit retreatment options. People who inject drugs (PWID) are the main driver of the HCV epidemic and are at highest risk for HCV transmission and reinfection. In this study, we report on RAVs at baseline (BL) and following virologic failure in treatment-naïve (TN) and -experienced (TE) methadone-maintained PWID.

    Methods: NS3/4A, NS5A and NS5B regions from the first 69 of 150 genotype 1a and 1b (GT1a/b) viruses from PWID in a trial examining 3 models of care for HCV treatment between 11/2013 and 11/2015 were sequenced based on anticipated DAA regimen. Antiviral agents included interferon (IFN), ribavirin (RBV), simeprevir (SMV), sofosbuvir (SOF), and ledipasvir (LDV). Variants relative to genotype/subtype specific H77 (GT1a) and Con1 (GT1b) reference sequences were reported.

    Results: We studied 69 HCV GT1a (N=65) and GT1b (N=5) infected PWID. Regimens included SMV/SOF N=12, SOF/RBV ± IFN N=33, and SOF/LDV N=24. Of the 65 (94.2%) TN PWID, 18/65 (27.7%) had RAVs at BL – 9/12 (75%) NS3, 7/24 (29.2%) NS5A, 2/65 (3.1%) NS5B. RAVs included: NS3 V36M/L N=2, T54S N=1, V55A/I N=3, Q80K/L N=5, I132V N=1; NS5A M28V N=4, L31M N=1, H54Y N=1, H58P N=1; NS5B S556G/R N=2. Of the 4 TE patients, 1 had a BL Q80K. Six (8.7%) patients failed therapy – 1 SMV/SOF, 3 SOF/RBV, 2 SOF/LDV. Only the SMV/SOF failure had a BL RAV (Q80K). This patient became HCV RNA positive at 24 weeks at which time a different set of viral variants were observed and the Q80K was no longer present. RAVs were not detected following SOF/RBV failure. Both SOF/LDV failures had NS5A mutations (Q30H/R, Y93H) post-BL.

    Conclusion: RAVs were present among a subset of TN PWID, particularly in NS3. Some RAVs appeared enriched compared to expected prevalence in DAA-naïve individuals. The BL RAVs observed did not affect treatment outcomes. One possible reinfection event was observed based on pre/post-BL variants. Re-treatment options may be limited among patients who fail SOF/LDV given selection of NS5A RAVs. The potential for transmitted NS5A RAVs could pose a particular concern for treatment of PWID.

    Matthew Akiyama, MD, MSc1, Jacqueline Reeves, PhD2, Yolanda Lie, BA2, Linda Agyemang, MPH1 and Alain Litwin, MD, MPH, MS1, (1)Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, (2)Monogram Biosciences, Laboratory Corporation of America Holdings, San Francisco, CA


    M. Akiyama, Gilead Sciences: Grant Investigator , Grant recipient

    J. Reeves, Monogram Biosciences: Employee and Shareholder , Salary

    Y. Lie, Monogram Biosciences: Employee , Salary

    L. Agyemang, None

    A. Litwin, Gilead Sciences: Scientific Advisor , Consulting fee and Research grant
    Merck Pharmaceuticals: Scientific Advisor , Consulting fee and Research grant
    Bristol-Myers Squibb: Scientific Advisor , Consulting fee
    Janssen Pharmaceutica: Scientific Advisor , Consulting fee
    Abbvie: Scientific Advisor , Consulting fee

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