Unboosted fosamprenavir is associated with low drug exposure in HIV-infected patients with mild-moderate liver impairment resulting from HCV-related cirrhosis.
OBJECTIVE
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 C(trough), AUC(0-12) 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%), C(trough) 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.
Gatti
Francesca
F
Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. francesca_gatti1@virgilio.it
Nasta
Paola
P
Loregian
Arianna
A
Puoti
Massimo
M
Matti
Alessandro
A
Pagni
Silvana
S
de Requena
Daniel Gonzalez
DG
Prestini
Katiela
K
Parisi
Saverio G
SG
Bonora
Stefano
S
Palù
Giorgio
G
Carosi
Giampiero
G
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002219:Carbamates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D054459:Elasticity Imaging Techniques; D005260:Female; D005663:Furans; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010949:Plasma / Q000737:chemistry; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019562:Viral Load
D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D010755:Organophosphates; D013449:Sulfonamides; D000410:Alanine Transaminase; C426859:fosamprenavir