Pegylated
interferon is active against both hepatitis C virus
(HCV) and HIV in laboratory studies and
in coinfected patients, according to a report published in the September 2007
issue of AIDS.
The major antiviral effect of interferon alpha on
HCV is blocking production of new virions (virus particles) from infected cells,
the authors wrote as background. In the present study, they investigated interferon's
previously unclear mechanism of action against HIV.
The researchers assessed
HIV and HCV viral kinetics and their relationship to interferon pharmacokinetics
in 9 coinfected patients with HCV genotype 1 during treatment with 1.5
mcg/kg/week pegylated interferon alpha-2b (PegIntron) plus 1000-1200 mg/day ribavirin.
In vivo modeling predictions of suppression of HIV replication by pegylated interferon
in CD8-depleted peripheral blood mononuclear cells were then verified by in vitro
experiments.
Results
•
HCV
and HIV showed different viral decline patterns after administration of pegylated
interferon.
•
Unlike
the biphasic decline of HCV, HIV showed a slow, continuous decline during the
first week, with no rebound when pegylated interferon levels declined.
•
Fitting
of HIV kinetics with known half-lives of free virus and infected cells indicated
that the major effect of interferon on HIV is blocking infection of new cells,
rather than inhibiting virion production.
•
The
magnitude of the antiviral effect against HIV was similar to that of antiretroviral
drugs (mean 1.1 log decline in HIV RNA at 7 days), but showed an inverse correlation
with baseline viremia.
•
In
vitro studies demonstrated that pre-incubating cell cultures with interferon led
to greater suppression of HIV replication than treating the cells after infection.
Conclusion
Based
on these findings, the authors wrote, "The complimentary antiviral properties
of interferon-alpha and antiretroviral therapy suggest a role for pharmacokinetically
improved formulations of interferon as part of salvage therapy for HIV-infected
individuals."
Bar-Ilan University, Ramat-Gan, Israel; NIDDK, National
Institutes of Health, Bethesda, MD; NIAID, National Institutes of Health, Bethesda,
MD; NCI, Frederick, MD; Clinical Research Center, National Institutes of Health,
Bethesda, MD; Erasmus Medical Center, Rotterdam, the Netherlands.
10/12/07
Reference A
Neumann, M Polis, L Rozenberg, and others. Differential antiviral effect of PEG-interferon-alpha-2b
on HIV and HCV in the treatment of HIV/HCV co-infected patients. AIDS 21(14):
1855-1865. September 2007.
