JAC Advance Access originally published online on January 16, 2009
Journal of Antimicrobial Chemotherapy 2009 63(3):575-578; doi:10.1093/jac/dkn525
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Original research |
Unboosted fosamprenavir is associated with low drug exposure in HIV-infected patients with mild–moderate liver impairment resulting from HCV-related cirrhosis
1 Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy 2 Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, Padua, Italy 3 Department of Infectious Diseases, University of Turin, Turin, Italy
Received 1 July 2008; returned 19 August 2008; revised 29 September 2008; accepted 7 December 2008
* Corresponding author. Tel: +39-030-3995665; Fax: +39-030-303061; E-mail: francesca_gatti1{at}virgilio.it
Objectives: The aim of this study was to compare amprenavir pharmacokinetics in HIV/hepatitis C virus (HCV)-co-infected cirrhotic patients receiving non-boosted fosamprenavir 700 mg twice daily with HCV/HIV-co-infected non-cirrhotic subjects and HIV-mono-infected subjects receiving fosamprenavir/ritonavir 700/100 mg twice daily. Liver stiffness at baseline and alanine aminotransferase levels at baseline and during follow-up were measured in order to find a correlation between drug levels and liver fibrosis or hepatotoxicity.
Methods: Amprenavir plasma concentration was determined by HPLC. Liver stiffness was measured by transient elastometry. Liver function tests were determined every 1–3 months during follow-up.
Results: Nineteen HIV-infected patients were included. Eight had chronic HCV hepatitis (group NC), five had HCV-related liver cirrhosis (group C) and six were HIV-mono-infected (group M). In group C patients, amprenavir Ctrough, AUC0–12 and half-life were 86%/83%, 64%/55% and 58%/59% lower when compared with controls and co-infected subjects without cirrhosis, respectively; conversely, drug clearance in cirrhotics was 181%/124% higher. In 3/5 cirrhotic patients (60%) and in 2/14 non-cirrhotic patients (14%), Ctrough was below the minimum target concentration of 400 ng/mL; nonetheless, in all these patients, HIV viral load was undetectable. No correlation was found between amprenavir pharmacokinetics and liver stiffness or hepatotoxicity at follow-up.
Conclusions: On the basis of these data, it seems reasonable to boost fosamprenavir with ritonavir even in cirrhotic patients; amprenavir pharmacokinetics could not be predicted by liver stiffness and seem not to predict hepatotoxicity at follow-up.
Keywords: pharmacokinetics , protease inhibitors , antiretrovirals , co-infection
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  M. Lanzafame, E. Lattuada, and F. Corsini Comment on: Unboosted fosamprenavir is associated with low drug exposure in HIV-infected patients with mild-moderate liver impairment resulting from HCV-related cirrhosis J. Antimicrob. Chemother., July 1, 2009; 64(1): 215 - 216. [Full Text] [PDF]
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F. Gatti, M. Puoti, P. Nasta, S. G. Parisi, and G. Carosi Unboosted fosamprenavir is associated with low drug exposure in HIV-infected patients with mild-moderate liver impairment resulting from HCV-related cirrhosis--authors' response J. Antimicrob. Chemother., July 1, 2009; 64(1): 216 - 216. [Full Text] [PDF]
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