BACKGROUND/AIMS: To gain understanding of inter-individual differences of treatment response in hepatitis C virus genotype 1 (HCV-G1) patients, we investigated simultaneously the early HCV kinetics and virus-specific T-cell reactivity. METHODS: Thirty, treatment-naïve HCV-G1 patients received peginterferon-alfa2a 180 microg/week plus ribavirin 1000-1200 mg/day, with blood samples collected prospectively at protocol time-points. HCV RNA was quantitated with a TaqMan assay with mathematical modelling of HCV decay. Virus-specific CD4+/CD8+ T-cells were enumerated by Elispot assays. RESULTS: HCV kinetic analysis identified two subgroups: fast (18/30) and slow (12/30) treatment-responders. Although these subgroups did not differ in any baseline characteristics, fast responders (FR) showed greater antiviral efficacy (epsilon) than slow responders (SR) (84.5+/-3.2 vs. 65.2+/-7.0%, P=0.002), and a higher rate of infected cell loss (delta) (0.56+/-0.2 vs. 0.04+/-0.02, P=0.038). The viral load drop (baseline to treatment week 4) was higher in FR vs. SR group (3.5+/-1.1 vs. 1.4+/-0.6 log10IU/mL, P<0.001). T-cell reactivity to HCV increased only in FR (after the loss of viraemia), but not in SR patients. CONCLUSIONS: Assessment of early viral and T-cell kinetics during treatment reveals marked differences amongst HCV-G1 patients and may provide a basis for treatment individualization. Enhancement of antiviral T-cell reactivity requires rapid viraemia clearance, rather than immunostimulation alone.
BACKGROUND/AIMS: To gain understanding of inter-individual differences of treatment response in hepatitis C virus genotype 1 (HCV-G1) patients, we investigated simultaneously the early HCV kinetics and virus-specific T-cell reactivity. METHODS: Thirty, treatment-naïve HCV-G1patients received peginterferon-alfa2a 180 microg/week plus ribavirin 1000-1200 mg/day, with blood samples collected prospectively at protocol time-points. HCV RNA was quantitated with a TaqMan assay with mathematical modelling of HCV decay. Virus-specific CD4+/CD8+ T-cells were enumerated by Elispot assays. RESULTS: HCV kinetic analysis identified two subgroups: fast (18/30) and slow (12/30) treatment-responders. Although these subgroups did not differ in any baseline characteristics, fast responders (FR) showed greater antiviral efficacy (epsilon) than slow responders (SR) (84.5+/-3.2 vs. 65.2+/-7.0%, P=0.002), and a higher rate of infected cell loss (delta) (0.56+/-0.2 vs. 0.04+/-0.02, P=0.038). The viral load drop (baseline to treatment week 4) was higher in FR vs. SR group (3.5+/-1.1 vs. 1.4+/-0.6 log10IU/mL, P<0.001). T-cell reactivity to HCV increased only in FR (after the loss of viraemia), but not in SR patients. CONCLUSIONS: Assessment of early viral and T-cell kinetics during treatment reveals marked differences amongst HCV-G1patients and may provide a basis for treatment individualization. Enhancement of antiviral T-cell reactivity requires rapid viraemia clearance, rather than immunostimulation alone.
Authors: Leland J Yee; KyungAh Im; Abdus S Wahed; Teodorica Bugawan; Jia Li; Shannon L Rhodes; Henry Erlich; Hugo R Rosen; T Jake Liang; Huiying Yang Journal: Antimicrob Agents Chemother Date: 2008-10-13 Impact factor: 5.191
Authors: Adam J Gehring; Dianxing Sun; Patrick T F Kennedy; Esther Nolte-'t Hoen; Seng Gee Lim; Shanthi Wasser; Clare Selden; Mala K Maini; Dan M Davis; Michael Nassal; Antonio Bertoletti Journal: J Virol Date: 2007-01-03 Impact factor: 5.103
Authors: Curtis L Cooper; Navneet K Ahluwalia; Susan M Efler; Jörg Vollmer; Arthur M Krieg; Heather L Davis Journal: J Immune Based Ther Vaccines Date: 2008-06-09