Abstract
BackgroundRibavirin (RBV) is an essential component of most current hepatitis C (HCV) treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN) to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR).MethodsWe included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS) participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT) 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24) and IL28B genotype (CC versus CT/TT).ResultsSVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80]) and ≥2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73]), regardless of treatment phase, and IL28B genotype.ConclusionIn HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype.
Highlights
According to the World Health Organization, more than 185 million people globally have been infected with hepatitis C virus (HCV) [1]
Patients with sustained virological response (SVR) had similar RBV concentrations compared to patients without SVR in both HCV genotype groups
SVR was not associated with RBV levels 2.0 mg/L (GT 1/4, odds ratio (OR) 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80]) and 2.5 mg/L (GT 1/ 4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73]), regardless of treatment phase, and IL28B genotype
Summary
According to the World Health Organization, more than 185 million people globally have been infected with hepatitis C virus (HCV) [1]. The combination of ribavirin (RBV) and pegylated interferon (pegIFN) was the standard of care for treatment of chronic HCV infection. PegIFN/RBV remains standard of care in in resource limited settings because of financial constraints [1]. RBV dose reduction and discontinuation are associated with reduced sustained virological response (SVR) rates [3]. Despite weight-adjusted dose regimens, interindividual RBV plasma concentrations vary widely [4, 5]. Ribavirin (RBV) is an essential component of most current hepatitis C (HCV) treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN) to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR)
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