Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study

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.

Peg‐interferon and ribavirin treatment in HIV/HCV co‐infected patients in Thailand: efficacy, safety and pharmacokinetics

“…We showed that at week 8 of treatment, ribavirin reached steady‐state, which fits the long elimination half‐life of 300 h . The steady‐state ribavirin plasma concentrations found in this study were in the same range as previously published in HIV/HCV co‐infected patients . However, these plasma concentrations remained lower than reported ribavirin plasma concentrations in mono‐infected patients .…”

“…This could be driven by the increasing number of patients of which ribavirin plasma concentrations were available towards weekend 48. The relation between ribavirin plasma concentrations and SVR remains controversial, as both negative and positive results have been published about this topic . These inconsistent results might be caused by, for example, differences in treatment, heterogeneity of populations, variation in analytical assays and small sample sizes.…”

“…Study visits were planned at baseline and week 1 (optional), 2,4,8,12,16,20,24,30,36,42 and 48 of treatment. In addition, 24 weeks after treatment had ended (week 72), the patient came to the study centre for determination of sustained virological response (SVR24).…”

Ribavirin Concentrations, Laboratory Variables, and Clinical Outcomes During Treatment of Hepatitis C Infection with First Generation Direct-Acting Antivirals

“…Inter-individual differences in RBV disposition are well documented and common side-effects, such as anaemia, have been associated with high RBV exposure [3]. Studies have suggested that positive treatment outcomes and adverse events may be associated with RBV concentration thresholds [4] but contradictory data exist [5], perhaps consistent with its multiple mechanisms of action [6,7]. The instability of drug concentrations in collected samples [8] further complicates RBV therapeutic monitoring.…”

Ribavirin steady‐state plasma level is a predictor of sustained virological response in hepatitis C–infected patients treated with direct‐acting antivirals

“…Studies investigating the association between RBV steady‐state plasma level and sustained virological response (SVR) in HCV mono‐ and HIV/HCV co‐infected patients show contradictory results, possibly due to their small sample sizes and retrospective nature . Moreover, studies on RBV steady‐state plasma levels in DAA‐treated patients are scarce.…”