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Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

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

Authors: Giorgiana Hatu, François Bailly, Emmanuel Pourcelot, Pierre Pradat, Patrick Miailhes, Marianne Maynard, François Parant, Pierre Chiarello, Jean-Michel Livrozet, Fabien Zoulim, Marie-Claude Gagnieu

Published in: BMC Infectious Diseases | Issue 1/2014

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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 AUC0-4h values observed in the more immunosuppressed coinfected patients.
Literature
1.
go back to reference Sherman KE, Rouster SD, Chung RT, Rajicic N: Hepatitis C Virus prevalence among patients infected with Human Immunodeficiency Virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group. Clin Infect Dis. 2002, 34 (6): 831-837. 10.1086/339042.CrossRefPubMed Sherman KE, Rouster SD, Chung RT, Rajicic N: Hepatitis C Virus prevalence among patients infected with Human Immunodeficiency Virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group. Clin Infect Dis. 2002, 34 (6): 831-837. 10.1086/339042.CrossRefPubMed
2.
go back to reference Sulkowski MS, Moore RD, Mehta SH, Chaisson RE, Thomas DL: Hepatitis C and progression of HIV disease. JAMA. 2002, 288 (2): 199-206. 10.1001/jama.288.2.199.CrossRefPubMed Sulkowski MS, Moore RD, Mehta SH, Chaisson RE, Thomas DL: Hepatitis C and progression of HIV disease. JAMA. 2002, 288 (2): 199-206. 10.1001/jama.288.2.199.CrossRefPubMed
3.
go back to reference Thomas DL, Vlahov D, Solomon L, Cohn S, Taylor E, Garfein R, Nelson KE: Correlates of hepatitis C virus infections among injection drug users. Medicine (Baltimore). 1995, 74 (4): 212-220. 10.1097/00005792-199507000-00005.CrossRef Thomas DL, Vlahov D, Solomon L, Cohn S, Taylor E, Garfein R, Nelson KE: Correlates of hepatitis C virus infections among injection drug users. Medicine (Baltimore). 1995, 74 (4): 212-220. 10.1097/00005792-199507000-00005.CrossRef
4.
go back to reference Rosenthal E, Poiree M, Pradier C, Perronne C, Salmon-Ceron D, Geffray L, Myers RP, Morlat P, Pialoux G, Pol S, Cacoub P: Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study). AIDS. 2003, 17 (12): 1803-1809. 10.1097/00002030-200308150-00009.CrossRefPubMed Rosenthal E, Poiree M, Pradier C, Perronne C, Salmon-Ceron D, Geffray L, Myers RP, Morlat P, Pialoux G, Pol S, Cacoub P: Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study). AIDS. 2003, 17 (12): 1803-1809. 10.1097/00002030-200308150-00009.CrossRefPubMed
5.
go back to reference Soriano V, Martin-Carbonero L, Garcia-Samaniego J, Puoti M: Mortality due to chronic viral liver disease among patients infected with human immunodeficiency virus. Clin Infect Dis. 2001, 33 (10): 1793-1795. 10.1086/323009.CrossRefPubMed Soriano V, Martin-Carbonero L, Garcia-Samaniego J, Puoti M: Mortality due to chronic viral liver disease among patients infected with human immunodeficiency virus. Clin Infect Dis. 2001, 33 (10): 1793-1795. 10.1086/323009.CrossRefPubMed
6.
go back to reference Clinical Practice Guidelines EASL: Management of hepatitis C virus infection. J Hepatol. 2014, 60 (2): 392-420.CrossRef Clinical Practice Guidelines EASL: Management of hepatitis C virus infection. J Hepatol. 2014, 60 (2): 392-420.CrossRef
7.
go back to reference Lindahl K, Stahle L, Bruchfeld A, Schvarcz R: High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C. Hepatology. 2005, 41 (2): 275-279. 10.1002/hep.20563.CrossRefPubMed Lindahl K, Stahle L, Bruchfeld A, Schvarcz R: High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C. Hepatology. 2005, 41 (2): 275-279. 10.1002/hep.20563.CrossRefPubMed
8.
go back to reference Rendon AL, Nunez M, Romero M, Barreiro P, Martin-Carbonero L, Garcia-Samaniego J, Jimenez-Nacher I, Gonzalez-Lahoz J, Soriano V: Early monitoring of ribavirin plasma concentrations may predict anemia and early virologic response in HIV/hepatitis C virus-coinfected patients. J Acquir Immune Defic Syndr. 2005, 39 (4): 401-405. 10.1097/01.qai.0000170034.90438.68.CrossRefPubMed Rendon AL, Nunez M, Romero M, Barreiro P, Martin-Carbonero L, Garcia-Samaniego J, Jimenez-Nacher I, Gonzalez-Lahoz J, Soriano V: Early monitoring of ribavirin plasma concentrations may predict anemia and early virologic response in HIV/hepatitis C virus-coinfected patients. J Acquir Immune Defic Syndr. 2005, 39 (4): 401-405. 10.1097/01.qai.0000170034.90438.68.CrossRefPubMed
9.
go back to reference Crespo M, Pou L, Esteban JI, Falco V, Ribera E, Lopez R, Sauleda S, Curran A, Villar Del Saz S, Feijoo M, Ocana I, Pahissa A: Early monitoring of ribavirin serum concentration is not useful to optimize hepatitis C virus treatment in HIV-coinfected patients. Antivir Ther. 2007, 12 (8): 1217-1223.PubMed Crespo M, Pou L, Esteban JI, Falco V, Ribera E, Lopez R, Sauleda S, Curran A, Villar Del Saz S, Feijoo M, Ocana I, Pahissa A: Early monitoring of ribavirin serum concentration is not useful to optimize hepatitis C virus treatment in HIV-coinfected patients. Antivir Ther. 2007, 12 (8): 1217-1223.PubMed
10.
go back to reference Jen J, Laughlin M, Chung C, Heft S, Affrime MB, Gupta SK, Glue P, Hajian G: Ribavirin dosing in chronic hepatitis C: application of population pharmacokinetic-pharmacodynamic models. Clin Pharmacol Ther. 2002, 72 (4): 349-361. 10.1067/mcp.2002.127112.CrossRefPubMed Jen J, Laughlin M, Chung C, Heft S, Affrime MB, Gupta SK, Glue P, Hajian G: Ribavirin dosing in chronic hepatitis C: application of population pharmacokinetic-pharmacodynamic models. Clin Pharmacol Ther. 2002, 72 (4): 349-361. 10.1067/mcp.2002.127112.CrossRefPubMed
11.
go back to reference Glue P: The clinical pharmacology of ribavirin. Semin Liver Dis. 1999, 19 (Suppl 1): 17-24.PubMed Glue P: The clinical pharmacology of ribavirin. Semin Liver Dis. 1999, 19 (Suppl 1): 17-24.PubMed
12.
go back to reference Jen JF, Glue P, Gupta S, Zambas D, Hajian G: Population pharmacokinetic and pharmacodynamic analysis of ribavirin in patients with chronic hepatitis C. Ther Drug Monit. 2000, 22 (5): 555-565. 10.1097/00007691-200010000-00010.CrossRefPubMed Jen JF, Glue P, Gupta S, Zambas D, Hajian G: Population pharmacokinetic and pharmacodynamic analysis of ribavirin in patients with chronic hepatitis C. Ther Drug Monit. 2000, 22 (5): 555-565. 10.1097/00007691-200010000-00010.CrossRefPubMed
13.
go back to reference Larrat S, Stanke-Labesque F, Plages A, Zarski JP, Bessard G, Souvignet C: Ribavirin quantification in combination treatment of chronic hepatitis C. Antimicrob Agents Chemother. 2003, 47 (1): 124-129. 10.1128/AAC.47.1.124-129.2003.CrossRefPubMedPubMedCentral Larrat S, Stanke-Labesque F, Plages A, Zarski JP, Bessard G, Souvignet C: Ribavirin quantification in combination treatment of chronic hepatitis C. Antimicrob Agents Chemother. 2003, 47 (1): 124-129. 10.1128/AAC.47.1.124-129.2003.CrossRefPubMedPubMedCentral
14.
go back to reference Wade JR, Snoeck E, Duff F, Lamb M, Jorga K: Pharmacokinetics of ribavirin in patients with hepatitis C virus. Br J Clin Pharmacol. 2006, 62 (6): 710-714. 10.1111/j.1365-2125.2006.02704.x.CrossRefPubMedPubMedCentral Wade JR, Snoeck E, Duff F, Lamb M, Jorga K: Pharmacokinetics of ribavirin in patients with hepatitis C virus. Br J Clin Pharmacol. 2006, 62 (6): 710-714. 10.1111/j.1365-2125.2006.02704.x.CrossRefPubMedPubMedCentral
15.
go back to reference Bruchfeld A, Lindahl K, Schvarcz R, Stahle L: Dosage of ribavirin in patients with hepatitis C should be based on renal function: a population pharmacokinetic analysis. Ther Drug Monit. 2002, 24 (6): 701-708. 10.1097/00007691-200212000-00004.CrossRefPubMed Bruchfeld A, Lindahl K, Schvarcz R, Stahle L: Dosage of ribavirin in patients with hepatitis C should be based on renal function: a population pharmacokinetic analysis. Ther Drug Monit. 2002, 24 (6): 701-708. 10.1097/00007691-200212000-00004.CrossRefPubMed
16.
go back to reference Dahari H, Markatou M, Zeremski M, Haller I, Ribeiro RM, Licholai T, Perelson AS, Talal AH: Early ribavirin pharmacokinetics, HCV RNA and alanine aminotransferase kinetics in HIV/HCV co-infected patients during treatment with pegylated interferon and ribavirin. J Hepatol. 2007, 47 (1): 23-30. 10.1016/j.jhep.2007.01.027.CrossRefPubMedPubMedCentral Dahari H, Markatou M, Zeremski M, Haller I, Ribeiro RM, Licholai T, Perelson AS, Talal AH: Early ribavirin pharmacokinetics, HCV RNA and alanine aminotransferase kinetics in HIV/HCV co-infected patients during treatment with pegylated interferon and ribavirin. J Hepatol. 2007, 47 (1): 23-30. 10.1016/j.jhep.2007.01.027.CrossRefPubMedPubMedCentral
17.
go back to reference Loustaud-Ratti V, Alain S, Rousseau A, Hubert IF, Sauvage FL, Marquet P, Denis F, Lunel F, Cales P, Lefebvre A, Fauchais AL, Liozon E, Vidal E: Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C. Hepatology. 2008, 47 (5): 1453-1461. 10.1002/hep.22217.CrossRefPubMed Loustaud-Ratti V, Alain S, Rousseau A, Hubert IF, Sauvage FL, Marquet P, Denis F, Lunel F, Cales P, Lefebvre A, Fauchais AL, Liozon E, Vidal E: Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C. Hepatology. 2008, 47 (5): 1453-1461. 10.1002/hep.22217.CrossRefPubMed
18.
go back to reference Arab-Alameddine M, Fayet-Mello A, Lubomirov R, Neely M, di Iulio J, Owen A, Boffito M, Cavassini M, Gunthard HF, Rentsch K, Buclin T, Aouri M, Telenti A, Decosterd LA, Rotger M, Csajka C: Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals. Antimicrob Agents Chemother. 2012, 56 (6): 2959-2966. 10.1128/AAC.05424-11.CrossRefPubMedPubMedCentral Arab-Alameddine M, Fayet-Mello A, Lubomirov R, Neely M, di Iulio J, Owen A, Boffito M, Cavassini M, Gunthard HF, Rentsch K, Buclin T, Aouri M, Telenti A, Decosterd LA, Rotger M, Csajka C: Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals. Antimicrob Agents Chemother. 2012, 56 (6): 2959-2966. 10.1128/AAC.05424-11.CrossRefPubMedPubMedCentral
19.
go back to reference Sauvage FL, Stanke-Labesque F, Gagnieu MC, Jourdil JF, Babany G, Marquet P: Feasibility of ribavirin therapeutic drug monitoring in hepatitis C. Ther Drug Monit. 2009, 31 (3): 374-381. 10.1097/FTD.0b013e3181a665e3.CrossRefPubMedPubMedCentral Sauvage FL, Stanke-Labesque F, Gagnieu MC, Jourdil JF, Babany G, Marquet P: Feasibility of ribavirin therapeutic drug monitoring in hepatitis C. Ther Drug Monit. 2009, 31 (3): 374-381. 10.1097/FTD.0b013e3181a665e3.CrossRefPubMedPubMedCentral
20.
go back to reference Aguilar Marucco D, Gonzalez De Requena D, Bonora S, Tettoni C, Bonasso M, De Blasi T, D'Avolio A, Sciandra M, Siccardi M, Baietto L, Trentini L, Sinicco A, Cariti G, Di Perri G: 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. J Antimicrob Chemother. 2008, 61 (4): 919-924. 10.1093/jac/dkn013.CrossRefPubMed Aguilar Marucco D, Gonzalez De Requena D, Bonora S, Tettoni C, Bonasso M, De Blasi T, D'Avolio A, Sciandra M, Siccardi M, Baietto L, Trentini L, Sinicco A, Cariti G, Di Perri G: 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. J Antimicrob Chemother. 2008, 61 (4): 919-924. 10.1093/jac/dkn013.CrossRefPubMed
21.
go back to reference Piedoux S, Monnet E, Piroth L, Montange D, Royer B, Thevenot T, Kantelip JP, Di Martino V, Muret P: Relative impact of ribavirin monitoring and HIV coinfection on sustained virological response in patients with chronic hepatitis C. Antivir Ther. 2011, 16 (8): 1317-1326. 10.3851/IMP1920.CrossRefPubMed Piedoux S, Monnet E, Piroth L, Montange D, Royer B, Thevenot T, Kantelip JP, Di Martino V, Muret P: Relative impact of ribavirin monitoring and HIV coinfection on sustained virological response in patients with chronic hepatitis C. Antivir Ther. 2011, 16 (8): 1317-1326. 10.3851/IMP1920.CrossRefPubMed
22.
23.
go back to reference Souvignet C, Maynard M, Gagnieu MC, Trepo C: Ribavirin in combination therapy for HCV chronic infection in HIV patients: how to win the war after winning the first battle?. J Hepatol. 2007, 47 (1): 1-3.CrossRefPubMed Souvignet C, Maynard M, Gagnieu MC, Trepo C: Ribavirin in combination therapy for HCV chronic infection in HIV patients: how to win the war after winning the first battle?. J Hepatol. 2007, 47 (1): 1-3.CrossRefPubMed
24.
go back to reference Carrat F, Bani-Sadr F, Pol S, Rosenthal E, Lunel-Fabiani F, Benzekri A, Morand P, Goujard C, Pialoux G, Piroth L, Salmon-Ceron D, Degott C, Cacoub P, Perronne C: Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA. 2004, 292 (23): 2839-2848. 10.1001/jama.292.23.2839.CrossRefPubMed Carrat F, Bani-Sadr F, Pol S, Rosenthal E, Lunel-Fabiani F, Benzekri A, Morand P, Goujard C, Pialoux G, Piroth L, Salmon-Ceron D, Degott C, Cacoub P, Perronne C: Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA. 2004, 292 (23): 2839-2848. 10.1001/jama.292.23.2839.CrossRefPubMed
25.
go back to reference Nunez M, Miralles C, Berdun MA, Losada E, Aguirrebengoa K, Ocampo A, Arazo P, Cervantes M, de Los SI, San Joaquin I, Echeverria S, Galindo MJ, Asensi V, Barreiro P, Sola J, Hernandez-Burruezo JJ, Guardiola JM, Romero M, Garcia-Samaniego J, Soriano V: Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses. 2007, 23 (8): 972-982. 10.1089/aid.2007.0011.CrossRefPubMed Nunez M, Miralles C, Berdun MA, Losada E, Aguirrebengoa K, Ocampo A, Arazo P, Cervantes M, de Los SI, San Joaquin I, Echeverria S, Galindo MJ, Asensi V, Barreiro P, Sola J, Hernandez-Burruezo JJ, Guardiola JM, Romero M, Garcia-Samaniego J, Soriano V: Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses. 2007, 23 (8): 972-982. 10.1089/aid.2007.0011.CrossRefPubMed
27.
go back to reference Lafeuillade A, Hittinger G, Chadapaud S: Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection. Lancet. 2001, 357 (9252): 280-281. 10.1016/S0140-6736(00)03618-7.CrossRefPubMed Lafeuillade A, Hittinger G, Chadapaud S: Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection. Lancet. 2001, 357 (9252): 280-281. 10.1016/S0140-6736(00)03618-7.CrossRefPubMed
28.
go back to reference Moreno A, Quereda C, Moreno L, Perez-Elias MJ, Muriel A, Casado JL, Antela A, Dronda F, Navas E, Barcena R, Moreno S: High rate of didanosine-related mitochondrial toxicity in HIV/HCV-coinfected patients receiving ribavirin. Antivir Ther. 2004, 9 (1): 133-138.PubMed Moreno A, Quereda C, Moreno L, Perez-Elias MJ, Muriel A, Casado JL, Antela A, Dronda F, Navas E, Barcena R, Moreno S: High rate of didanosine-related mitochondrial toxicity in HIV/HCV-coinfected patients receiving ribavirin. Antivir Ther. 2004, 9 (1): 133-138.PubMed
29.
go back to reference Soriano V, Puoti M, Sulkowski M, Cargnel A, Benhamou Y, Peters M, Mauss S, Brau N, Hatzakis A, Pol S, Rockstroh J: Care of patients coinfected with HIV and hepatitis C virus: 2007 updated recommendations from the HCV-HIV International Panel. AIDS. 2007, 21 (9): 1073-1089. 10.1097/QAD.0b013e3281084e4d.CrossRefPubMed Soriano V, Puoti M, Sulkowski M, Cargnel A, Benhamou Y, Peters M, Mauss S, Brau N, Hatzakis A, Pol S, Rockstroh J: Care of patients coinfected with HIV and hepatitis C virus: 2007 updated recommendations from the HCV-HIV International Panel. AIDS. 2007, 21 (9): 1073-1089. 10.1097/QAD.0b013e3281084e4d.CrossRefPubMed
Metadata
Title
Lower ribavirin biodisponibility in patients with HIV-HCV coinfection in comparison with HCV monoinfected patients
Authors
Giorgiana Hatu
François Bailly
Emmanuel Pourcelot
Pierre Pradat
Patrick Miailhes
Marianne Maynard
François Parant
Pierre Chiarello
Jean-Michel Livrozet
Fabien Zoulim
Marie-Claude Gagnieu
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-150

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