Higher plasma lopinavir concentrations are associated with a moderate rise in cholestasis markers in HIV-infected patients.
OBJECTIVE
The aim of this study was to evaluate the correlation between liver function markers (necrosis and cholestasis) and plasma lopinavir levels in a cohort of HIV-infected patients treated with lopinavir and ritonavir.


METHODS
The blood samples for determining steady-state C(trough) lopinavir levels and analysing liver function were drawn from fasting patients. Steady-state C(trough) lopinavir levels, liver function and immuno-virological markers were assessed on the same day. Plasma lopinavir and ritonavir levels were determined by means of high-performance liquid chromatography.


RESULTS
One hundred and forty-nine patients were included in the analysis [57 were HCV co-infected (34%) and 10 were HBV co-infected (6.7%)]; they had been treated with lopinavir/ritonavir for a median of 232 days (range 132-282). All patients received lopinavir/ritonavir [400/100 mg twice daily or 533/133 mg twice daily if amprenavir or a non-nucleoside reverse transcriptase inhibitor (NNRTI) was part of therapy] and concomitant therapy with NRTI(s). Median (interquartile) lopinavir trough levels were 6391 ng/mL (4121-8726), 5662 (3585-8893) and 6819 ng/mL (5324-8726) in the patients with HIV alone and those with HIV/HCV (or HBV) co-infection, respectively (P = not significant). Univariate analysis showed a significant association between the cholestasis markers and C(trough) lopinavir level. Multivariate analysis selected only gamma glutamyltranspeptidase (GGT) (OR = 1.010, 95% CI: 1.002-1.021) as being independently associated with plasma lopinavir levels of >6425 ng/mL; alkaline phosphatase (OR = 1.004, 95% CI: 1.000-1.010; P = 0.08) and total bilirubin (OR = 3.118, 95% CI: 0.980-11.715; P = 0.07) were not associated.


CONCLUSIONS
Elevated lopinavir concentrations are associated with raised GGT.
Seminari
Elena
E
Infectious Disease Department, San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20122 Milan, Italy. elena.seminari@hsr.it
Gentilini
Gianluca
G
Galli
Laura
L
Hasson
Hamid
H
Danise
Anna
A
Carini
Elisabetta
E
Dorigatti
Fernanda
F
Soldarini
Armando
A
Lazzarin
Andriano
A
Castagna
Antonella
A
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D019380:Anti-HIV Agents / Q000097:blood* / Q000493:pharmacokinetics; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000032:analysis; D002779:Cholestasis / Q000097:blood* / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012189:Retrospective Studies; D005723:gamma-Glutamyltransferase / Q000097:blood / Q000378:metabolism
D019380:Anti-HIV Agents; D015415:Biomarkers; D011744:Pyrimidinones; D061466:Lopinavir; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin