Late relapse versus hepatitis c virus reinfection in patients with sustained virologic response after sofosbuvir-based therapies

Christoph Sarrazin, Vasily Isakov, Evguenia S. Svarovskaia, Charlotte Hedskog, Ross Martin, Krishna Chodavarapu, Diana M. Brainard, Michael D. Miller, Hongmei Mo, Jean Michel Molina, Mark Sulkowski

Research output: Contribution to journalArticle

Abstract

Background. The development of direct-acting antivirals in recent years has dramatically enhanced rates of viral eradication to >90% in patients with chronic hepatitis C virus (HCV) infection. To determine true treatment efficacy and define the most appropriate retreatment, it is important to distinguish virologic relapse from reinfection when patients in whom HCV is eradicated during treatment become infected with a new HCV strain after treatment. Methods. We investigated the prevalence of late recurrent viremia (patients with sustained virologic response 12 weeks after the end of treatment but detectable HCV RNA at follow-up week 24) and used refined phylogenetic analysis of multiple HCV genes to distinguish virologic relapse from reinfection. Results. Across 11 phase 3 clinical trials of ledipasvir-sofosbuvir (SOF) and SOF, only 12 of 3004 patients had detectable HCV RNA following sustained virologic response 12 weeks after the end of treatment. Of these 12 patients with late recurrent viremia, 11 had the same HCV genotype/subtype at baseline and at recurrence. Phylogenetic analysis demonstrated that 58% (7 of 12) of these patients were successfully treated with the SOF-based regimen, with HCV eradication achieved, but became reinfected with a different HCV strain after treatment. The remaining 5 patients with late recurrent viremia had virologic relapse in which the HCV present at baseline persisted in the liver or another compartment and reemerged in the blood 24 weeks after treatment. Conclusions. The incidence of late recurrent viremia was low. Distinguishing reinfection from virologic relapse has implications for determining true treatment efficiency and selecting optimal retreatment strategies.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalClinical Infectious Diseases
Volume64
Issue number1
DOIs
StatePublished - 2017

Keywords

  • Hepatitis c virus
  • Late recurrent viremia
  • Reinfection
  • Sustained virologic response
  • Viologic relapse

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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    Sarrazin, C., Isakov, V., Svarovskaia, E. S., Hedskog, C., Martin, R., Chodavarapu, K., Brainard, D. M., Miller, M. D., Mo, H., Molina, J. M., & Sulkowski, M. (2017). Late relapse versus hepatitis c virus reinfection in patients with sustained virologic response after sofosbuvir-based therapies. Clinical Infectious Diseases, 64(1), 44-52. https://doi.org/10.1093/cid/ciw676