Hepatitis C Virus Cure in Human Immunodeficiency Virus Coinfection Dampens Inflammation and Improves Cognition Through Multiple Mechanisms

J Infect Dis. 2020 Jul 6;222(3):396-406. doi: 10.1093/infdis/jiaa109.

Abstract

Background: Chronic inflammation in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection increases cognitive impairment. With newer, direct-acting antiviral therapies for HCV, our objective was to determine whether chronic inflammation would be decreased and cognition improved with HCV sustained viral response (SVR) in coinfection.

Methods: We studied 4 groups longitudinally: 7 HCV-monoinfected and 12 HIV/HCV-coinfected persons before and after treatment for HCV, 12 HIV-monoinfected persons, and 9 healthy controls. We measured monocyte activation and gene expression, monocyte-derived exosome micro-ribonucleic acid (miRNA) expression, plasma inflammation, and cognitive impairment before and after therapy.

Results: Plasma soluble CD163 and neopterin were decreased in HCV mono- and coinfected persons. Blood CD16+ monocytes were decreased in coinfection after HCV treatment. Global deficit score improved 25% in coinfection with the visual learning/memory domain the most improved. Hepatitis C virus SVR decreased monocyte interferon genes MX1, IFI27, and CD169 in coinfection and MX1, LGALS3BP, and TNFAIP6 in HCV monoinfection. Monocyte exosomes from coinfected persons increased in microRNA (miR)-19a, miR-221, and miR-223, all of which were associated with decreasing inflammation and nuclear factor-κB activation.

Conclusions: Hepatitis C virus cure in coinfection brings monocyte activation to levels of HIV alone. Cognitive impairment is significantly improved with cure but not better than HIV infection alone, which strong suggests that cognitive impairment was driven by both HIV and HCV.SummaryHCV cure in HIV coinfection improves monocyte and plasma activation markers and increases cognitive function in the visual learning/memory domain.

Keywords: DAA therapy; HCV; HIV; exosomes; microRNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antigens, CD / blood
  • Antigens, Differentiation, Myelomonocytic / blood
  • Antiviral Agents / therapeutic use
  • Case-Control Studies
  • Cognition / drug effects
  • Cognition Disorders / blood
  • Cognition Disorders / complications*
  • Cognition Disorders / genetics
  • Cognition Disorders / virology
  • Coinfection / blood
  • Coinfection / drug therapy*
  • Female
  • Gene Expression
  • HIV Infections / blood
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Humans
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Neopterin / blood
  • Prospective Studies
  • Receptors, Cell Surface / blood

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antiviral Agents
  • CD163 antigen
  • Receptors, Cell Surface
  • Neopterin