Background:  Rapid viral response (RVR) has been identified as a useful predictor of treatment outcome among patients with hepatitis C virus (HCV) infection. Its utility in HCV-mono-infected and HCV/HIV-co-infected hemophilic subjects remains unexplored. We evaluated early predictors of viral response based upon viral kinetic modeling parameters from a prospective treatment trial.

Methods:  Hemophilic subjects with HCV or HCV/HIV co-infection were enrolled in a prospective trial, treated with pegylated interferon-alpha2a qw + ribavirin 800 mg once daily for 48 weeks, and followed for 24 weeks. Sustained viral response was defined as HCV RNA not detectable by polymerase chain reaction (PCR) at end of follow-up. RVR was defined as HCV RNA negative after 4 weeks of treatment. Viral kinetic parameters were calculated using data derived from serum samples collected at multiple time points during the first 28 days of treatment.

Results:  We enrolled 23 subjects in the trial:  12 were HCV mono-infected and 11 were co-infected. Most were male and Caucasian (91%). Mean age was 36.9 years; 10.5% had advanced fibrosis (F3-4); mean HCV viral load was 6.6 log₁₀ IU/mL prior to start of treatment. Genotype 1 or 4 was present in 65% of subjects. Median baseline CD4 was 746.4 cells/mm³ in monoinfected and 695 cells/mm³ in co-infected subjects. Sustained virologic response was achieved in 8 of 22 subjects (36.4%) who had detectable virus at the end of pre-treatment screening (1 subject was virus negative prior to first dose). Intent-to-treat analysis demonstrated sustained virologic response in 45.5% vs 27% of those with mono-infection and co-infection, respectively. RVR occurred in 9 subjects and was observed in 7 of 8 with sustained virologic response (87.5%) This association was highly significant (p = 0.0004). Viral kinetic parameters were estimable for 18 subjects. Best subset regression of calculated variables suggested strong RVR association with ε (viral efficacy) and  λ₂ (second phase decline slope). Mean epsilon was 0.926 (SEM = 0.067) among those with RVR and 0.53 (SEM = 0.12) among those without. λ₂ was also significantly greater among subjects with RVR (p = 0.006).

Conclusions:  RVR was highly predictive of sustained virologic response in both HCV mono-infected and co-infected hemophilic subjects. Kinetic modeling provided evidence for a strong association between RVR and early viral clearance efficacy (ε) and with phase 2 viral decline slope. Larger prospective trials may permit identification of response and non-response parameters within the first week of treatment.