A potent antiviral effect on hepatitis C viral dynamics in serum and peripheral blood mononuclear cells during combination therapy with high-dose daily interferon alfa plus ribavirin and intravenous twice-daily treatment with interferon beta

Hepatitis C virus (HCV) is known to infect and replicate within peripheral blood mononuclear cells (PBMC), thereby enabling the direct evaluation of a ntiviral mechanisms by analyzing HCV dynamics in PBMC. To address potential molecular differences associated with distinct antiviral regimens, we stud ied HCV dynamics in both serum and PBMC in 44 patients with HCV genotype Ib and high viral load who were randomly assigned to the following 4 differen t treatment groups: 1) combination therapyAdth 6 MU daily of interferon alf a 2b (IFN-alpha 2b) plus 800 mg of ribavirin; 2) monotherapy with 6 MU dail y of IFN-alpha 2b; 3) monotherapy with twice-daily intravenous administrati on with 3MU of IFN-beta; and 4) monotherapy with daily intravenous administ ration with 6 MU of IFN-beta. HCV-RNA levels were measured serially using h ighly sensitive real-time detection polymerase chain reaction (PCR). HCV dy namics in both the serum and PBMC showed a "biphasic" pattern. The exponent ial decay slopes of the second phase were significantly higher in the combi nation or twice-daily dosing regimen groups compared with groups 2 or 4 (0. 10 +/- 0.08 VS. 0.02 +/- 0.09 or 0.16 +/- 0.09 vs. 0.02 +/- 0.04 day(-1); P < .05 or P < .0005, respectively). Moreover, the viral half-lives in the s econd phase were significantly shorter in these groups (73.2 +/- 42.5 vs. 2 40.1 +/- 120.7 or 56.0 +/- 44.6 vs. 361.6 +/- 293.5 hours; P < .05 or P < . 05, respectively). Additionally, the slope of HCV decline in PBMC tended to be higher in the combination regimens, as compared with monotherapy. Taken together, our data on HCV dynamics provide molecular insight into utilizat ion of combination or twice-daily dosing regimens to increase rates of sust ained viral eradication of HCV.