Higher plasma lopinavir concentrations are associated with a moderate rise in cholestasis markers in HIV-infected patients

Elena Seminari, Gianluca Gentilini, Laura Galli, Hamid Hasson, Anna Danise, Elisabetta Carini, Fernanda Dorigatti, Armando Soldarini, Andriano Lazzarin, Antonella Castagna

Research output: Contribution to journalArticle

Abstract

Objectives: 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. Patients and methods: The blood samples for determining steady-state Ctrough lopinavir levels and analysing liver function were drawn from fasting patients. Steady-state Ctrough 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 Ctrough 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.

Original languageEnglish
Pages (from-to)790-792
Number of pages3
JournalJournal of Antimicrobial Chemotherapy
Volume56
Issue number4
DOIs
Publication statusPublished - Oct 2005

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Lopinavir
Cholestasis
HIV
Ritonavir
Liver
Reverse Transcriptase Inhibitors
Coinfection
Bilirubin
Alkaline Phosphatase
Fasting
Necrosis
Multivariate Analysis

Keywords

  • Drug monitoring
  • HIV antiviral pharmacology
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology

Cite this

Higher plasma lopinavir concentrations are associated with a moderate rise in cholestasis markers in HIV-infected patients. / Seminari, Elena; Gentilini, Gianluca; Galli, Laura; Hasson, Hamid; Danise, Anna; Carini, Elisabetta; Dorigatti, Fernanda; Soldarini, Armando; Lazzarin, Andriano; Castagna, Antonella.

In: Journal of Antimicrobial Chemotherapy, Vol. 56, No. 4, 10.2005, p. 790-792.

Research output: Contribution to journalArticle

Seminari, Elena ; Gentilini, Gianluca ; Galli, Laura ; Hasson, Hamid ; Danise, Anna ; Carini, Elisabetta ; Dorigatti, Fernanda ; Soldarini, Armando ; Lazzarin, Andriano ; Castagna, Antonella. / Higher plasma lopinavir concentrations are associated with a moderate rise in cholestasis markers in HIV-infected patients. In: Journal of Antimicrobial Chemotherapy. 2005 ; Vol. 56, No. 4. pp. 790-792.
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abstract = "Objectives: 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. Patients and methods: The blood samples for determining steady-state Ctrough lopinavir levels and analysing liver function were drawn from fasting patients. Steady-state Ctrough 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 Ctrough 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.",
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T1 - Higher plasma lopinavir concentrations are associated with a moderate rise in cholestasis markers in HIV-infected patients

AU - Seminari, Elena

AU - Gentilini, Gianluca

AU - Galli, Laura

AU - Hasson, Hamid

AU - Danise, Anna

AU - Carini, Elisabetta

AU - Dorigatti, Fernanda

AU - Soldarini, Armando

AU - Lazzarin, Andriano

AU - Castagna, Antonella

PY - 2005/10

Y1 - 2005/10

N2 - Objectives: 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. Patients and methods: The blood samples for determining steady-state Ctrough lopinavir levels and analysing liver function were drawn from fasting patients. Steady-state Ctrough 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 Ctrough 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.

AB - Objectives: 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. Patients and methods: The blood samples for determining steady-state Ctrough lopinavir levels and analysing liver function were drawn from fasting patients. Steady-state Ctrough 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 Ctrough 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.

KW - Drug monitoring

KW - HIV antiviral pharmacology

KW - Pharmacokinetics

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