JAC Advance Access published online on January 31, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn013
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Original research |
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
Department of Infectious Diseases, University of Turin, Turin, Italy
Received 7 September 2007; returned 21 December 2007; revised 22 October 2007; accepted 2 January 2008
* Corresponding author. Clinica Universitaria, Ospedale Amedeo di Savoia, Corso Svizzera 164, 10149 Torino, Italy. Tel: +39-011-4393980; Fax: +39-011-4393882; E-mail: diego.agui{at}libero.it
Objectives: To study the association between trough ribavirin concentration (Ctrough) 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 Ctrough 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 Ctrough and early virological response (EVR) nor SVR was found. However, in patients with genotype 1 or 4, ribavirin Ctrough was independently associated with EVR (P = 0.036) and SVR (P = 0.046). A ribavirin Ctrough cut-off of 1600 ng/mL was found to be associated with both EVR (
2 = 5.69, P = 0.028) and SVR (2=4.2, P = 0.04). Higher ribavirin Ctrough correlated with Hb decrease (R = –0.361, 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 Ctrough of >2300 ng/mL was associated with an Hb decrease of >4 g/dL (2 = 8.08, P = 0.01).
Conclusions: Our study confirmed a relationship between ribavirin exposure and both efficacy and toxicity. Moreover, we found ribavirin Ctrough cut-offs for both SVR in genotypes 1 and 4 and overall haematological toxicity. These findings deserve further clinical evaluation.
Key Words: anti-HCV therapy , therapeutic drug monitoring , cut-off values
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