Abstract
In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard-of-care (SOC) ribavirin dosing concurrent with pegIFN-α. Four weeks of ribavirin mono-therapy resulted in a mean 0.46 log10 IU/mL HCV RNA reduction differentially regulated across IL28B genotypes (0.89 vs. 0.21 log10 IU/mL for CC and CT/TT respectively; P = 0.006), increased likelihood of undetectable HCV RNA week 4 after initiating pegIFN-α and thus shortened treatment duration (P<0.05), and decreased median IP-10 concentration from 550 to 345 pg/mL (P<0.001). Both experimental strategies impacted on ribavirin concentrations, and high levels were achieved after one week of double dosing. However, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes.Trial RegistrationClinicalTrials.gov NCT01226771
Highlights
Therapy for hepatitis C virus (HCV) infection recently has undergone major improvements regarding therapeutic efficacy and reduction of side effects following the introduction of interferon-free regimens comprising combinations of direct acting antivirals (DAA) [1,2,3,4,5,6,7,8,9,10,11,12], often including the use of ribavirin
Neither a 4-week “priming” with ribavirin mono-therapy nor 2-weeks double dosing had any significant impact on the primary study endpoints, i.e. first and second phase decline, or on sustained virological response (SVR), consistent with several previous studies [37, 48], but contrasting with the study by Quiles-Pérez et al that noted an effect on early viral kinetics [36]
One should bear in mind that in addition to the decline in HCV RNA observed after 4 weeks of ribavirin mono-therapy, patients in the “priming” arm had a slightly lower baseline viral load, which in combination likely impacted on the likelihood of achieving very rapid virologic response (VRVR) and rapid virological response (RVR)
Summary
Therapy for hepatitis C virus (HCV) infection recently has undergone major improvements regarding therapeutic efficacy and reduction of side effects following the introduction of interferon-free regimens comprising combinations of direct acting antivirals (DAA) [1,2,3,4,5,6,7,8,9,10,11,12], often including the use of ribavirin. Ribavirin is insufficient to achieve clearance of HCV infection [19, 20], but in interferon-based combination therapy, it is pivotal to increase the likelihood of achieving a sustained virological response (SVR) by means of reduced relapse risk [21, 22]. Ribavirin monotherapy reportedly has a modest effect on HCV RNA, with mean reductions of approximately 0.5 log IU/mL, in addition to reducing systemic concentrations of liver enzymes [23]
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