Pegylated interferon-α2a treatment of chronic SIV-infected macaques

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: In vitro and clinical observations in HIV-infected patients receiving interferon α therapy have shown a reduction in HIV loads. Limited investigations have explored the innate or adaptive immune responses of IFN- α on SIV replication in vivo. Methods: Seven chronically infected rhesus macaques were given pegylated IFN-α 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-α levels for the initial period of therapy and IFN-α inducible antiviral molecules were increased sporadically in the PBMC mRNA of the treatment group. Despite the demonstrable effect of the IFN-α injections, the treatment had no effect on plasma viral RNA levels. Conclusions: This work demonstrates that while short term IFN-α 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-α therapy for the treatment of HIV will require macaque specific cytokines.

Original languageEnglish (US)
Pages (from-to)26-30
Number of pages5
JournalJournal of Medical Primatology
Volume37
Issue number1
DOIs
StatePublished - Feb 2008

Fingerprint

Macaca
interferons
Interferons
therapeutics
Innate Immunity
Therapeutics
HIV
Adaptive Immunity
injection
Antiviral Agents
mononuclear leukocytes
virus replication
viral load
Macaca mulatta
pharmacokinetics
Injections
cytokines
immunity
Viral RNA
RNA

Keywords

  • Innate immune responses
  • Interferon inducible molecules
  • Macaque
  • Pegylated interferon-α2a
  • Simian immunodeficiency virus (SIV)
  • TypeI interferons

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

Cite this

Pegylated interferon-α2a treatment of chronic SIV-infected macaques. / Asmuth, David; Abel, K.; George, M. D.; Dandekar, Satya; Pollard, Richard B; Miller, Chris J.

In: Journal of Medical Primatology, Vol. 37, No. 1, 02.2008, p. 26-30.

Research output: Contribution to journalArticle

@article{b7118eb5b90442b2b49f66573f41788f,
title = "Pegylated interferon-α2a treatment of chronic SIV-infected macaques",
abstract = "Background: In vitro and clinical observations in HIV-infected patients receiving interferon α therapy have shown a reduction in HIV loads. Limited investigations have explored the innate or adaptive immune responses of IFN- α on SIV replication in vivo. Methods: Seven chronically infected rhesus macaques were given pegylated IFN-α 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-α levels for the initial period of therapy and IFN-α inducible antiviral molecules were increased sporadically in the PBMC mRNA of the treatment group. Despite the demonstrable effect of the IFN-α injections, the treatment had no effect on plasma viral RNA levels. Conclusions: This work demonstrates that while short term IFN-α 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-α therapy for the treatment of HIV will require macaque specific cytokines.",
keywords = "Innate immune responses, Interferon inducible molecules, Macaque, Pegylated interferon-α2a, Simian immunodeficiency virus (SIV), TypeI interferons",
author = "David Asmuth and K. Abel and George, {M. D.} and Satya Dandekar and Pollard, {Richard B} and Miller, {Chris J}",
year = "2008",
month = "2",
doi = "10.1111/j.1600-0684.2007.00221.x",
language = "English (US)",
volume = "37",
pages = "26--30",
journal = "Journal of Medical Primatology",
issn = "0047-2565",
publisher = "Blackwell Munksgaard",
number = "1",

}

TY - JOUR

T1 - Pegylated interferon-α2a treatment of chronic SIV-infected macaques

AU - Asmuth, David

AU - Abel, K.

AU - George, M. D.

AU - Dandekar, Satya

AU - Pollard, Richard B

AU - Miller, Chris J

PY - 2008/2

Y1 - 2008/2

N2 - Background: In vitro and clinical observations in HIV-infected patients receiving interferon α therapy have shown a reduction in HIV loads. Limited investigations have explored the innate or adaptive immune responses of IFN- α on SIV replication in vivo. Methods: Seven chronically infected rhesus macaques were given pegylated IFN-α 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-α levels for the initial period of therapy and IFN-α inducible antiviral molecules were increased sporadically in the PBMC mRNA of the treatment group. Despite the demonstrable effect of the IFN-α injections, the treatment had no effect on plasma viral RNA levels. Conclusions: This work demonstrates that while short term IFN-α 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-α therapy for the treatment of HIV will require macaque specific cytokines.

AB - Background: In vitro and clinical observations in HIV-infected patients receiving interferon α therapy have shown a reduction in HIV loads. Limited investigations have explored the innate or adaptive immune responses of IFN- α on SIV replication in vivo. Methods: Seven chronically infected rhesus macaques were given pegylated IFN-α 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-α levels for the initial period of therapy and IFN-α inducible antiviral molecules were increased sporadically in the PBMC mRNA of the treatment group. Despite the demonstrable effect of the IFN-α injections, the treatment had no effect on plasma viral RNA levels. Conclusions: This work demonstrates that while short term IFN-α 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-α therapy for the treatment of HIV will require macaque specific cytokines.

KW - Innate immune responses

KW - Interferon inducible molecules

KW - Macaque

KW - Pegylated interferon-α2a

KW - Simian immunodeficiency virus (SIV)

KW - TypeI interferons

UR - http://www.scopus.com/inward/record.url?scp=38149027730&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38149027730&partnerID=8YFLogxK

U2 - 10.1111/j.1600-0684.2007.00221.x

DO - 10.1111/j.1600-0684.2007.00221.x

M3 - Article

VL - 37

SP - 26

EP - 30

JO - Journal of Medical Primatology

JF - Journal of Medical Primatology

SN - 0047-2565

IS - 1

ER -