Pegylated Interferon-α-Induced Natural Killer Cell Activation Is Associated With Human Immunodeficiency Virus-1 DNA Decline in Antiretroviral Therapy-Treated HIV-1/Hepatitis C Virus-Coinfected Patients

Clin Infect Dis. 2018 Jun 1;66(12):1910-1917. doi: 10.1093/cid/cix1111.

Abstract

Background: Interferon alpha (IFN-α) can potently reduce human immunodeficiency virus type 1 (HIV-1) replication in tissue culture and animal models, but may also modulate residual viral reservoirs that persist despite suppressive antiretroviral combination therapy. However, mechanisms leading to viral reservoir reduction during IFN-α treatment are unclear.

Methods: We analyzed HIV-1 gag DNA levels in CD4 T cells by digital droplet polymerase chain reaction and CD8 T-cell and natural killer (NK) cell phenotypes by flow cytometry in a cohort of antiretroviral therapy-treated HIV-1/hepatitis C virus-coinfected patients (n = 67) undergoing treatment for hepatitis C infection with pegylated IFN-α and ribavirin for an average of 11 months.

Results: We observed that IFN-α treatment induced a significant decrease in CD4 T-cell counts (P < .0001), in CD4 T-cell-associated HIV-1 DNA copies (P = .002) and in HIV-1 DNA copies per microliter of blood (P < .0001) in our study patients. Notably, HIV-1 DNA levels were unrelated to HIV-1-specific CD8 T-cell responses. In contrast, proportions of total NK cells, CD56brightCD16- NK cells, and CD56brightCD16+ NK cells were significantly correlated with reduced levels of CD4 T-cell-associated HIV-1 DNA during IFN-α treatment, especially when coexpressing the activation markers NKG2D and NKp30.

Conclusions: These data suggest that the reduction of viral reservoir cells during treatment with IFN-α is primarily attributable to antiviral activities of NK cells.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antiretroviral Therapy, Highly Active
  • Cohort Studies
  • Coinfection / drug therapy*
  • Coinfection / immunology
  • Coinfection / virology
  • DNA, Viral / blood*
  • Disease Reservoirs / virology
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • Hepacivirus / drug effects
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Spain
  • Viral Load
  • gag Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • DNA, Viral
  • Interferon-alpha
  • Recombinant Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a