Background &Aims: Kinetic modeling of hepatitis C virus(HCV) response to inte rferon (IFN)-based therapy provides insights into factors associated with treat ment outcomes.HCV/human immunodeficiency virus (HIV)-co...Background &Aims: Kinetic modeling of hepatitis C virus(HCV) response to inte rferon (IFN)-based therapy provides insights into factors associated with treat ment outcomes.HCV/human immunodeficiency virus (HIV)-co-infected patients show lower response rates vs. HCV-monoinfected patients. Reasons for this remain un clear. This study evaluated kinetic parameters and treatment responses in co-in fected vs monoinfected patients. Methods: Co-infected patients were randomized within a US multicenter trial (ACTG 5071) to receive pegylated-interferon (PEG -IFN) alfa-2a +ribavirin vs.IFN alfa-2a +ribavirin. Monoinfected controls w ere matched prospectively for treatment, genotype, age, sex, race, and histology .Quantitative HCV-RNA testing was performed at hours 0,6, 12, 24, 48, and 72; d ays 7, 10, 14, 28, and 56; and weeks 12,24, 48, and 72. Results: Twelve HCV/HIV -co-infected and 15 HCV-monoinfected patients underwent viral kinetic samplin g.Among HIV-positive patients the mean CD4+count was 325 cells/mm3. Seventy-f ive percent of patients were genotype 1.The HCV-RNA level was undetectable at 7 2 weeks in 25%and 40%of co-infected and monoinfected patients, respectively.P hase 1/2 declines, free virus clearance rate, and infected hepatocyte death rate were not affected by co-infection status but differed by treatment. Efficiency (e) ≥90%at 60 hours was associated with viral clearance (P =. 02). Modeling w ith pooled parameters suggests baseline viral load is a key factor in time to re sponse in this cohort. Predicted clearance time increased by 28%in co-infected patients. Conclusions: Co-infection status did not affect key kinetic paramete rs. Among kinetic parameters, efficiency was associated significantly with viral clearance. Co-infected patients may require longer treatment duration thanmono infected patients given their generally higher baseline viral loads.展开更多
文摘Background &Aims: Kinetic modeling of hepatitis C virus(HCV) response to inte rferon (IFN)-based therapy provides insights into factors associated with treat ment outcomes.HCV/human immunodeficiency virus (HIV)-co-infected patients show lower response rates vs. HCV-monoinfected patients. Reasons for this remain un clear. This study evaluated kinetic parameters and treatment responses in co-in fected vs monoinfected patients. Methods: Co-infected patients were randomized within a US multicenter trial (ACTG 5071) to receive pegylated-interferon (PEG -IFN) alfa-2a +ribavirin vs.IFN alfa-2a +ribavirin. Monoinfected controls w ere matched prospectively for treatment, genotype, age, sex, race, and histology .Quantitative HCV-RNA testing was performed at hours 0,6, 12, 24, 48, and 72; d ays 7, 10, 14, 28, and 56; and weeks 12,24, 48, and 72. Results: Twelve HCV/HIV -co-infected and 15 HCV-monoinfected patients underwent viral kinetic samplin g.Among HIV-positive patients the mean CD4+count was 325 cells/mm3. Seventy-f ive percent of patients were genotype 1.The HCV-RNA level was undetectable at 7 2 weeks in 25%and 40%of co-infected and monoinfected patients, respectively.P hase 1/2 declines, free virus clearance rate, and infected hepatocyte death rate were not affected by co-infection status but differed by treatment. Efficiency (e) ≥90%at 60 hours was associated with viral clearance (P =. 02). Modeling w ith pooled parameters suggests baseline viral load is a key factor in time to re sponse in this cohort. Predicted clearance time increased by 28%in co-infected patients. Conclusions: Co-infection status did not affect key kinetic paramete rs. Among kinetic parameters, efficiency was associated significantly with viral clearance. Co-infected patients may require longer treatment duration thanmono infected patients given their generally higher baseline viral loads.
