Pegylated interferon-alpha 2a treatment of chronic SIV-infected macaques.
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.
Asmuth
D M
DM
Division of Infectious Diseases, Department of Internal Medicine, University of California-Davis Medical Center, 4150 V Street, Sacramento, CA 95817, USA. david.asmuth@ucdmc.ucdavis.edu
Abel
K
K
George
M D
MD
Dandekar
S
S
Pollard
R B
RB
Miller
C J
CJ
D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008251:Macaca; D008992:Monkey Diseases / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D014766:Viremia; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a