Lower ribavirin biodisponibility in patients with HIV-HCV coinfection in comparison with HCV monoinfected patients.

Giorgiana Hatu 1, 2 François Bailly 3, 1 Emmanuel Pourcelot 4 Pierre Pradat 1, 3, * Patrick Miailhes 3, 5 Marianne Maynard 1, 3 François Parant 4 Pierre Chiarello 6 Jean-Michel Livrozet 6 Fabien Zoulim 1, 3 Marie-Claude Gagnieu 4
* Auteur correspondant
1 Service d'hépatologie
2 Université de Médicine et Pharmacie "Iuliu Hatieganu"
3 CRCL - Centre de Recherche en Cancérologie de Lyon
4 Pharmacologie
5 Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL]
6 Service d'immunologie
Abstract : BACKGROUND: In HIV infected patients, the impact of ribavirin (RBV) pharmacology on sustained virologic response (SVR) to hepatitis C virus (HCV) treatment has not been fully investigated. The objective of this study was to compare the early RBV plasma exposure between a population of HIV-HCV coinfected patients and an HCV monoinfected group. METHODS: Early RBV plasma exposure (expressed as Area Under the Curve (AUC) from 0 to 4 h) after a 600 mg first dose of RBV was measured in a population of HIV-HCV coinfected patients in comparison with an HCV monoinfected group. Peripheral blood samples were collected before the 600 mg RBV first dose (T0) to ensure no detectable baseline plasma RBV, and then 30 mn, 1, 2 and 4 hours after RBV intake (T0.5, T1, T2 and T4). RESULTS: Eighty-six patients with chronic hepatitis C entered the study among whom 23 (27%) were HIV-HCV coinfected. Coinfected patients had a significantly lower RBV-AUC(0-4h) (median: 1469 μg*h/L [range 936-3677]) compared with monoinfected patients (2030 μg*h/L [851-7700]; p = 0.018). This RBV under exposure in coinfected patients persisted after normalization of AUC to RBV dose per kilogram of body weight (182 μg*h/L [110-425] versus 271 μg*h/L [82-1091], p = 0.001). CONCLUSIONS: These results suggest that lower early bioavailability of RBV could be one of the reasons for lower SVR in HIV-HCV coinfected patients treated with pegylated interferon/RBV combination therapy. RBV plasma underexposure seems to be associated with the immunological status of the patients with lower AUC(0-4h) values observed in the more immunosuppressed coinfected patients.
Keywords : Hepatitis C Human immunodeficiency virus Ribavirin exposure Treatment Coinfection
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BMC Infectious Diseases, BioMed Central, 2014, 14 (1), pp.150. 〈10.1186/1471-2334-14-150〉
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Giorgiana Hatu, François Bailly, Emmanuel Pourcelot, Pierre Pradat, Patrick Miailhes, et al.. Lower ribavirin biodisponibility in patients with HIV-HCV coinfection in comparison with HCV monoinfected patients.. BMC Infectious Diseases, BioMed Central, 2014, 14 (1), pp.150. 〈10.1186/1471-2334-14-150〉. 〈inserm-00981317〉

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