Background:  Hemophilic patients with HCV, with or without HIV co-infection, are at increased risk of liver disease progression. There are limited data regarding treatment response in patients with inherited clotting disorders. Viral kinetic modeling may provide insights into factors affecting response to treatment. This study compares viral kinetics during the first two weeks of treatment in co-infected vs mono-infected hemophiliacs.

Methods: Hemophilic patients with either HCV or HCV/HIV co-infection from 4 tertiary centers were enrolled in a treatment trial. All were given PEG-IFN-α 2a (180 mg every week) + ribavirin (800 mg once daily). Quantitative HCV RNA (Roche COBAS Amplicor) testing was performed at hours 0, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 72, 96, and days 7 and 14 post-treatment initiation. HIV RNA viral load was measured at baseline (bDNA, Bayer Diagnostics). A mathematical model was used to calculate parameters associated with HCV clearance.

Results:  Of 21 patients who underwent viral kinetic sampling, 10 were co-infected subjects (10 male) and 11 were mono-infected controls (9 male, 2 female). Mean ages were 35.5 and 38.6 years, respectively. Median CD4 counts were 641 and 724 cells/mm³, respectively. Six co-infected patients had baseline HIV RNA <75 copies/mL. Mean log HCV VL was 6.7 IU/mL for co-infected vs. 6.3 IU/mL for controls. Six subjects in each group were genotype 1. Two co-infected patients had HCV VL <600 IU/mL on day 14, vs 6 controls (median days to clearance = 14 and 3.5, respectively). Treatment efficacy in blocking viral production (ε) and slope of phase 2 viral decline (λ₂) were calculated.

Both infection status and genotype were highly associated with probability of clearance (p = 0.001 and 0.005). CD4 and baseline HCV viral load were not predictive of clearance; neither was λ₂ after controlling for genotype. For pts who cleared within 2 weeks, the model’s predicted days to clearance correlated well with actual (r = 0.874, p = 0.01, Spearman) and ε correlated negatively with time to clearance (r = -0.867, p = 0.01, Spearman).

Conclusions:  Regression models suggest that co-infection and genotype are key predictors of early treatment response in HCV-infected hemophiliacs. This outcome may be related to a trend toward slower phase 1 decline (ε) and a decreased λ₂ slope in co-infected subjects.

Keywords: kinetics; hemophilia; HCV/HIV