Improvement of Gut Diversity and Composition After Direct-Acting Antivirals in Hepatitis C Virus-Infected Patients With or Without Human Immunodeficiency Virus Coinfection

J Infect Dis. 2021 Oct 28;224(8):1410-1421. doi: 10.1093/infdis/jiab094.

Abstract

Background: The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)-infected patients with or without human immunodeficiency virus (HIV) is unclear.

Methods: We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir-grazoprevir from a clinical trial. Fecal specimens collected before treatment and 12 weeks after treatment were analyzed using amplicon-based 16S ribosomal RNA sequencing.

Results: Sustained virological response rates in the monoinfection and coinfection groups were similar (98.4% vs 95.8%). Pretreatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha diversity but decreased Firmicutes-Bacteroidetes ratios. The improvement of microbial dysbiosis was observed in responders achieving sustained virological response across fibrosis stages but was not found in nonresponders. Responders with a low degree of fibrosis exhibited a recovery in alpha diversity to levels comparable to those in healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders.

Conclusions: This study indicates a short-term effect of direct-acting antivirals in restoration of microbial dysbiosis. The favorable changes in gut microbiota profiles after viral eradication might contribute toward the reduction of HCV-related complications among infected individuals.

Keywords: 16S rRNA; DAAs; HCV; HIV; SVR; gut microbiota.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Benzofurans / therapeutic use*
  • Coinfection / drug therapy*
  • Drug Combinations
  • Drug-Related Side Effects and Adverse Reactions
  • Dysbiosis / complications
  • Dysbiosis / drug therapy*
  • Female
  • Gastrointestinal Microbiome*
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Hepacivirus
  • Hepatitis C / complications
  • Hepatitis C / drug therapy*
  • Humans
  • Imidazoles / therapeutic use*
  • Male
  • Middle Aged
  • Quinoxalines / therapeutic use*
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • Benzofurans
  • Drug Combinations
  • Imidazoles
  • Quinoxalines
  • elbasvir-grazoprevir drug combination