Pegylated interferon-alpha 2a treatment of chronic SIV-infected macaques

J Med Primatol. 2008 Feb;37(1):26-30. doi: 10.1111/j.1600-0684.2007.00221.x.

Abstract

Background: In vitro and clinical observations in HIV-infected patients receiving interferon alpha therapy have shown a reduction in HIV loads. Limited investigations have explored the innate or adaptive immune responses of IFN-alpha on SIV replication in vivo.

Methods: Seven chronically infected rhesus macaques were given pegylated IFN-alpha 2a (n = four) or saline (n = three) injections once weekly for 14 weeks. Weekly peripheral blood samples were taken for safety parameters, viral load determinations, and measurements of innate and adaptive immune responses.

Results: Pharmacokinetic measurements demonstrated therapeutic peg-IFN-alpha levels for the initial period of therapy and IFN-alpha inducible antiviral molecules were increased sporadically in the PBMC mRNA of the treatment group. Despite the demonstrable effect of the IFN-alpha injections, the treatment had no effect on plasma viral RNA levels.

Conclusions: This work demonstrates that while short term IFN-alpha therapy induces innate antiviral immunity, it does not dramatically enhance or suppress viral replication. However, studies in the SIV model to determine therapeutic potential of chronic IFN-alpha therapy for the treatment of HIV will require macaque specific cytokines.

Publication types

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

MeSH terms

  • Animals
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Interferon alpha-2
  • Interferon-alpha / pharmacokinetics
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use*
  • Macaca*
  • Monkey Diseases / drug therapy*
  • Polyethylene Glycols / pharmacokinetics
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins
  • Simian Acquired Immunodeficiency Syndrome / drug therapy*
  • Viremia
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • peginterferon alfa-2a