The use of trough ribavirin concentration to predict sustained virological response and haematological toxicity in HIV/HCV-co-infected patients treated with ribavirin and pegylated interferon

Objectives: To study the association between trough ribavirin concentration (C-trough) with sustained virological response (SVR) and haemoglobin (Hb) decrease in HIV/hepatitis C virus (HCV)-co-infected (HIV+/HCV+) patients treated with anti-HCV therapy. Methods: HIV+/HCV+ patients treated with ribavirin and pegylated interferon were prospectively evaluated. Qualitative and quantitative HCV- RNA, Hb levels and ribavirin C-trough were measured at baseline and weeks 2, 4, 12, 24, 36 and 48 during therapy. HCV- RNA was also measured at 24 weeks after the end of therapy. Efficacy analysis was performed on patients with a definitive virological outcome (SVR, relapser and non-responder), whereas for toxicity analysis, dropouts were considered until the last available observation. Results: Fifty-two patients (54.7% with genotype 1 or 4) were included. Overall, no correlation between ribavirin C-trough and early virological response (EVR) nor SVR was found. However, in patients with genotype 1 or 4, ribavirin C-trough was independently associated with EVR (P = 0.036) and SVR (P = 0.046). A ribavirin C-trough cut-off of 1600 ng/mL was found to be associated with both EVR (chi(2) = 5.69, P = 0.028) and SVR (chi(2) = 4.2, P = 0.04). Higher ribavirin C-trough correlated with Hb decrease (R = 20.361, P = 0.009) and was independently associated with an Hb decrease of > 4 g/dL (P = 0.009). Receiver operating characteristic (ROC) analysis indicated that a ribavirin C-trough of > 2300 ng/mL was associated with an Hb decrease of > 4 g/dL (chi(2) = 8.08, P = 0.01). Conclusions: Our study confirmed a relationship between ribavirin exposure and both efficacy and toxicity. Moreover, we found ribavirin C-trough cut-offs for both SVR in genotypes 1 and 4 and overall haematological toxicity. These findings deserve further clinical evaluation.