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

J Infect Dis. 2020 Sep 14;222(8):1334-1344. doi: 10.1093/infdis/jiaa254.

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.

Clinical trials registration: NCT02194998.

Keywords: DAA therapy; hepatitis C; human; immunity; inflammation.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 2-Naphthylamine
  • Adult
  • Anilides / therapeutic use
  • Anti-HIV Agents / therapeutic use
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Carbamates / therapeutic use
  • Coinfection / drug therapy*
  • Coinfection / immunology
  • Cyclopropanes / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV-1 / drug effects
  • Hepacivirus / drug effects
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / immunology
  • Humans
  • Immunologic Factors / blood
  • Lactams, Macrocyclic / therapeutic use
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / immunology
  • Male
  • Middle Aged
  • Proline / analogs & derivatives
  • Proline / therapeutic use
  • Ribavirin / therapeutic use
  • Ritonavir / therapeutic use
  • Sulfonamides / therapeutic use
  • Sustained Virologic Response
  • Uracil / analogs & derivatives
  • Uracil / therapeutic use
  • Valine

Substances

  • Anilides
  • Anti-HIV Agents
  • Antiviral Agents
  • Biomarkers
  • Carbamates
  • Cyclopropanes
  • Immunologic Factors
  • Lactams, Macrocyclic
  • Sulfonamides
  • ombitasvir
  • Ribavirin
  • Uracil
  • Proline
  • 2-Naphthylamine
  • dasabuvir
  • Valine
  • Ritonavir
  • paritaprevir

Associated data

  • ClinicalTrials.gov/NCT02194998