Estimation of early hepatitis C viral clearance in patients receiving daily interferon and ribavirin therapy using a mathematical model.
Patients with hepatitis C virus (HCV) genotype 1 infection are resistant to standard interferon (IFN) therapy. We used a mathematical model to estimate the duration of daily therapy necessary to maximize the number of patients achieving viral negativity before 12 weeks of therapy. Patients from a study to determine HCV RNA reduction over 4 weeks using 3 million units (MU), 5 MU, or 10 MU of IFN alfa daily plus Ribavirin were compared with a group receiving IFN alfa 3 MU three times a week. By extending the linear regression and prediction interval lines, the estimated time to negativity was greater than 12 weeks for the standard IFN group, 42 to greater than 84 days for the 3 MU IFN daily plus Ribavirin, 39 to 60 days for 5 MU IFN daily plus Ribavirin and 25 to 45 days for the 10 MU IFN daily and Ribavirin group, respectively. Thus, the use of a predictive model based on log transformation and linear regression of the early HCV RNA response suggests daily doses of 5 or 10 million units of IFN plus Ribavirin will be theoretically necessary for longer than 4 weeks to maximize the number of patients who clear virus by 12 weeks of therapy. This model may be useful in predicting response in groups of patients receiving other therapies.
Bekkering
F C
FC
Department of Hepatogastroenterology, University Hospital Rotterdam, The Netherlands.
Stalgis
C
C
McHutchison
J G
JG
Brouwer
J T
JT
Perelson
A S
AS
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D012254:Ribavirin / Q000627:therapeutic use*; D019562:Viral Load
D000998:Antiviral Agents; D012254:Ribavirin; D007372:Interferons