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IFN-free therapy is associated with restoration of type I IFN response in HIV-1 patients with acute HCV infection who achieve SVR.

Publication ,  Journal Article
Carlton-Smith, C; Holmes, JA; Naggie, S; Lidofsky, A; Lauer, GM; Kim, AY; Chung, RT; of the ACTG A5327 study group,
Published in: J Viral Hepat
May 2018

Interferon (IFN)-free direct-acting antiviral agents (DAAs) have revolutionized chronic hepatitis C virus (HCV) treatment; early studies suggest excellent efficacy in acute HCV. However, changes in innate immune responses during DAA therapy for acute HCV are unknown. We studied interferon-stimulated gene (ISG) expression and related cytokines/chemokines in HIV-infected patients with acute HCV receiving sofosbuvir plus ribavirin (SOF+RBV) as part of the A5327 clinical trial. ISG expression was determined from PBMCs, and circulating cytokines/chemokines were quantified from serum from study participants. The overall sustained virologic response (SVR) was 57%; all treatment failures were due to virologic relapse. Apart from NOS2a, baseline ISG/chemokine/cytokine levels were similar irrespective of treatment outcome. Downregulation of ISGs was observed at treatment week four and end of treatment (EOT), implicating HCV in establishing elevated ISGs early during HCV infection. Levels of many of these ISGs increased at post-treatment week 12 (PTW12) in relapsers only, coinciding with recurrent HCV RNA. Eleven ISGs were differentially expressed in responders vs relapsers. On-treatment viral suppression was also associated with a reduction in IP-10, CXCL11 and MIP-1β levels. In contrast, circulating IFN-α levels were significantly higher at EOT and PTW12 in responders vs relapsers. Upregulation of peripheral ISG expression is established early in the course of HCV infection during acute HCV infection, but did not predict subsequent treatment outcome with SOF+RBV. ISGs were downregulated during therapy and increased post-therapy in relapsers. IFN-α levels were higher in responders at EOT/PTW12, suggesting that impaired type I IFN production/secretion may contribute to relapse.

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Published In

J Viral Hepat

DOI

EISSN

1365-2893

Publication Date

May 2018

Volume

25

Issue

5

Start / End Page

465 / 472

Location

England

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Sustained Virologic Response
  • Sofosbuvir
  • Ribavirin
  • Middle Aged
  • Male
  • Interferon Type I
  • Immunologic Factors
  • Humans
 

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Carlton-Smith, C., Holmes, J. A., Naggie, S., Lidofsky, A., Lauer, G. M., Kim, A. Y., … of the ACTG A5327 study group, . (2018). IFN-free therapy is associated with restoration of type I IFN response in HIV-1 patients with acute HCV infection who achieve SVR. J Viral Hepat, 25(5), 465–472. https://doi.org/10.1111/jvh.12836
Carlton-Smith, C., J. A. Holmes, S. Naggie, A. Lidofsky, G. M. Lauer, A. Y. Kim, R. T. Chung, and R. T. of the ACTG A5327 study group. “IFN-free therapy is associated with restoration of type I IFN response in HIV-1 patients with acute HCV infection who achieve SVR.J Viral Hepat 25, no. 5 (May 2018): 465–72. https://doi.org/10.1111/jvh.12836.
Carlton-Smith C, Holmes JA, Naggie S, Lidofsky A, Lauer GM, Kim AY, et al. IFN-free therapy is associated with restoration of type I IFN response in HIV-1 patients with acute HCV infection who achieve SVR. J Viral Hepat. 2018 May;25(5):465–72.
Carlton-Smith, C., et al. “IFN-free therapy is associated with restoration of type I IFN response in HIV-1 patients with acute HCV infection who achieve SVR.J Viral Hepat, vol. 25, no. 5, May 2018, pp. 465–72. Pubmed, doi:10.1111/jvh.12836.
Carlton-Smith C, Holmes JA, Naggie S, Lidofsky A, Lauer GM, Kim AY, Chung RT, of the ACTG A5327 study group. IFN-free therapy is associated with restoration of type I IFN response in HIV-1 patients with acute HCV infection who achieve SVR. J Viral Hepat. 2018 May;25(5):465–472.
Journal cover image

Published In

J Viral Hepat

DOI

EISSN

1365-2893

Publication Date

May 2018

Volume

25

Issue

5

Start / End Page

465 / 472

Location

England

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Sustained Virologic Response
  • Sofosbuvir
  • Ribavirin
  • Middle Aged
  • Male
  • Interferon Type I
  • Immunologic Factors
  • Humans