BACKGROUND: High dose interferon induction treatment of hepatitis C viral
infection blocks viral production over 95%. Since dose reduction is often
performed due to clinical considerations, the effect of dose reduction on
hepatitis C virus kinetics was studied. METHODS: A new model that allowed
longitudinal changes in the parameters of viral dynamics was used in a
group of genotype-1 patients (N = 15) with dose reduction from 10 to 3
million units of interferon daily in combination with ribavirin, in
comparison to a control group (N = 9) with no dose reduction. RESULTS:
Dose reduction gave rise to a complex viral kinetic pattern, which could
be only explained by a decrease in interferon effectiveness in blocking
virion production. The benefit of the rapid initial viral decline
following the high induction dose is lost after dose reduction. In
addition, in some patients also the second phase viral decline slope,
which is highly predictive of success of treatment, was impaired by the
dose reduction resulting in smaller percentage of viral clearance in the
dose reduction group. CONCLUSIONS: These findings, while explaining the
failure of many induction schedules, suggest that for genotype-1 patients
induction therapy should be continued till HCVRNA negativity in serum in
order to increase the sustained response rate for chronic hepatitis C