Hepatitis C: Viral kinetics

Estimation of Early Hepatitis C Viral Clearance in Patients Receiving Daily Interferon and Ribavirin Therapy Using A Mathematical Model

“…We propose that both the rapid and the slower phase of viral decline 5,7 are important for reaching viral negativity: a patient with an extremely large first phase viral decline will reach undetectable levels of HCV RNA much earlier than someone with a minimal first phase viral load decline, assuming both have the same second phase of viral decline. Because it is rare for a patient to reach viral negativity during the first phase, the slope of the second phase will ultimately determine if someone reaches negativity.…”

“…Because the second phase generally includes all data from the second day of treatment onward, use of only second-phase data has been shown to provide a good prediction for viral negativity of individual patients at 12 weeks 7 and thus should be sufficient to determine the expected duration of daily therapy to reach viral negativity. 5 The linear regression model that we have proposed can be used with the combined data of both phases or with data of the second phase alone. In our study, 2 measurements of HCV RNA before 2 days of treatment (0.5 and 1 day) and 8 points of the slower second phase were included in the overall model, leading to a prediction interval that did not differ significantly from an evaluation including only the second phase.…”

“…(Because viral loads fall many orders of magnitude when effective therapy is given, log transformation is used so that data at high and low viral loads have more equivalent weight in the linear regression analysis.) First, we included data from both the early first phase of viral decline, as previously reported [5][6][7] to observe the linear regression of phase 1 and 2 combined. Second, we included only data from the second phase (viral load data after 48 hours after treatment initiation) to test the hypothesis that the slope of the second phase alone can be used to predict treatment duration until viral negativity is reached, and to test whether the second phase of viral reduction follows an exponential decline as previously described.…”

“…Second, we included only data from the second phase (viral load data after 48 hours after treatment initiation) to test the hypothesis that the slope of the second phase alone can be used to predict treatment duration until viral negativity is reached, and to test whether the second phase of viral reduction follows an exponential decline as previously described. 5 Using this software, 95% confidence intervals were also calculated for these linear regression lines for the 4 groups. Mathematically, the model is very simple: y ϭ at ϩ b, where t is treatment time, y ϭ log transformed viral load data, a ϭ the calculated slope of viral decline, and b ϭ log transformed viral load at t ϭ 0.…”

“…[4][5][6][7][8] Also, an acute dose response has been reported with higher daily doses of IFN in chronic hepatitis C, and a biphasic exponential viral decline has been described in chronic HCV infection during therapy. [5][6][7] In addition, most patients who achieve a sustained virologic response to antiviral therapy do so early during treatment (in general before week 12), [9][10][11][12][13] and a greater than 3 log reduction in serum HCV RNA early during therapy has been reported to be a good predictor of eventual sustained response. 14 Early clearance of HCV may also theoretically prevent the development of resistant quasispecies.…”