3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

THE IMPACT OF CO-INFECTION WITH HEPATITIS C OR HEPATITIS B ON LOPINAVIR PHARMACOKINETICS IN PATIENTS INFECTED WITH HIV

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. WePe3.2C06

Dickinson L.¹, Micheli V.², Meraviglia P.², Tjia J.¹, Almond L.¹, Regazzi M.³, Back D.¹, Cargnel A.^2
1University of Liverpool, Liverpool, United Kingdom, ²Sacco Hospital, Milan, Italy, ³IRCCS-Policlinico S. Matteo, Pavia, Italy

INTRODUCTION: Protease inhibitors-based regimens can induce hepatotoxicity. Liver disease may alter the pharmacokinetics (PK) of antiretrovirals that under-go hepatic metabolism and could produce changes in plasma protein binding. The protease inhibitor lopinavir (LPV) is a cytochrome P450 substrate and highly bound to plasma proteins (98 – 99%). The aim of this study was to evaluate LPV total and unbound PK in HIV-infected patients with and without HCV/HBV co-infection.

METHODS: Forty-one patients receiving boosted lopinavir (LPV/RTV: 400/100mg bid, n=33; 533/133mg bid, n=3; 266/66mg bid, n=5) therapy [14 HIV+ controls; 27 HCV/HBV co-infected (7/27 cirrhotic); 10 females; median (range) age 43 years (32 – 64)] participated in the study. LPV PK assessment was performed at steady-state. Bound and unbound LPV were separated by ultrafiltration and total and unbound LPV concentrations quantified by a validated HPLC-UV and HPLC-MS/MS method, respectively. Total and unbound LPV area under the curve over the dosing interval (AUCTOTAL and AUCUB, respectively) was calculated (non-compartmental analysis; WinNonlin). AUCUB was expressed as a percentage of AUCTOTAL (%AUCUB). Differences in PK between patients with and without HCV/HBV co-infection were evaluated (Mann-Whitney U test).

RESULTS: Thirty-nine patients were included in the analysis (13 HIV+ controls; 26 HCV/HBV co-infected). Median (range) AUCTOTAL, AUCUB and %AUCUB for HIV+ controls and HCV/HBV co-infected patients were 107150 (61069 – 149908) and 92114 ng.h/mL (33160 – 204750), 851 (510 – 1657) and 1073 ng.h/mL (413 – 2181), 0.96% (0.35 – 1.19) and 1.02% (0.60 – 2.22), respectively. There were no statistically significant differences in AUCTOTAL, AUCUB and %AUCUB between study groups (p=0.51, 0.53 and 0.18, respectively). AUCTOTAL, AUCUB and %AUCUB in cirrhotic patients were 87130 ng.h/mL, 821 ng.h/mL and 1.11%; these were not statistically different to controls (p=0.35, 0.77, 0.31, respectively).

CONCLUSIONS: In the cohort of patients studied, LPV total and unbound PK was not affected by hepatic impairment. Given the small number of cirrhotic patients, further studies are warranted to characterise LPV PK in this group.

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050724
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