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Immune-based
Experimental HCV Therapy Isatoribine Significantly Reduces
HCV RNA levels
Immune-based
therapy is the mainstay treatment for chronic hepatitis C virus (HCV) infection
but causes multiple side effects and achieves durable viral
clearance in only approximately 50% of patients. Most new
investigational anti-HCV compounds are direct-acting antivirals
for which durability of response and risk of viral mutations
and resistance are not yet known.
Therefore,
continuing discovery and development of new immune-based
treatments is desirable. Toll-like receptors
(TLRs) are pathogen recognition receptors that initiate the
innate immune response. The responsiveness of HCV or other
ongoing chronic systemic infections to treatment with a selective
TLR agonist has not been reported.
Isatoribine is a selective agonist of TLR7. In a proof-of-concept
study, researchers found that once-daily 7-day treatment with
intravenous isatoribine 800 mg caused a significant (P
= .001) reduction of plasma HCV RNA (mean, -0.76; range, -2.85
to +0.21 log10 units) in otherwise untreated patients
(n = 12) who were chronically infected with HCV.
Viral
load reduction occurred in patients infected with genotype
1 as well as non-genotype
1 HCV. The reduction of viral load was correlated
with induction of markers of a heightened immune antiviral
state.
The
treatment was well tolerated, with a low frequency of mild
to moderate adverse
events. In conclusion, the authors write, “Systemic
administration of the selective TLR7 agonist isatoribine resulted
in dose-dependent changes in immunologic biomarkers and a
statistically significant antiviral effect with relatively
few and mild side effects.”
08/26/05
Reference
Y
Horsmans and others. Isatoribine, an agonist of TLR7, reduces
plasma virus concentration in chronic hepatitis C infection.
Hepatology 42: 724-731. September 2005.
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