Hepatitis C Virus (HCV) direct-acting antiviral therapy in persons with human immunodeficiency virus-HCV genotype 1 coinfection resulting in high rate of sustained virologic response and variable in normalization of soluble markers of immune activation

Donald D. Anthony, Mark S. Sulkowski, Laura M. Smeaton, Sofi Damjanovska, Carey L. Shive, Corinne M. Kowal, Daniel E. Cohen, Debika Bhattacharya, Beverly L. Alston-Smith, Ashwin Balagopal, David L. Wyles

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Hepatitis C virus (HCV) direct-acting antivirals are highly effective. Less is known about changes in markers of immune activation in persons with human immunodeficiency virus (HIV) in whom a sustained virologic response (SVR) is achieved. Methods: We conducted a nonrandomized clinical trial of 12 or 24 weeks of paritaprevir-ritonavir-ombitasvir plus dasabuvir (PrOD) with or without ribavirin in persons with HCV-1/HIV coinfection suppressed with antiretroviral therapy. Plasma HCV, soluble CD14 (sCD14), interferon-inducible protein 10, soluble CD163 (sCD163), interleukin 6 (IL-6), interleukin 18, monocyte chemoattractant protein (MCP-1), autotaxin (ATX), and Mac2-binding protein (Mac2BP) were measured over 48 weeks. Results: Participants were treated with PrOD for 12 (n = 9) or 24 (n = 36) weeks; the SVR rate at 12 weeks was 93%. At baseline, cirrhosis was associated with higher ATX and MCP-1, female sex with higher ATX and IL-6, older age with higher Mac2BP, higher body mass index with higher ATX, and HIV-1 protease inhibitor use with higher sCD14 levels. In those with SVR, interferon-inducible protein 10, ATX, and Mac2BP levels declined by week 2, interleukin 18 levels declined by the end of treatment, sCD14 levels did not change, and sCD163, MCP-1, and IL-6 levels changed at a single time point. Conclusions: During HIV/HCV coinfection, plasma immune activation marker heterogeneity is in part attributable to age, sex, cirrhosis, body mass index, and/or type of antiretroviral therapy. HCV treatment with paritaprevir-ritonavir-ombitasvir plus dasabuvir is highly effective and is associated with variable rate and magnitude of decline in markers of immune activation.

Original languageEnglish (US)
Pages (from-to)1334-1344
Number of pages11
JournalJournal of Infectious Diseases
Volume222
Issue number8
DOIs
StatePublished - Oct 15 2020

Keywords

  • DAA therapy
  • Hepatitis C
  • Human
  • Immunity
  • Inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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