Ezetimibe, a promising lipid-lowering agent for the treatment of dyslipidaemia in HIV-infected patients with poor response to statins

Eugenia Negredo, José Moltó, Jordi Puig, Denise Cinquegrana, Anna Bonjoch, Núria Pérez-Álvarez, Raquel López-Blázquez, Asunción Blanco, Bonaventura Clotet, Celestino Rey-Joly

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To assess the efficacy, safety, and pharmacokinetic interactions of ezetimibe in HIV-infected patients with poorly controlled antiretroviral-associated dyslipidaemia while taking pravastatin alone. DESIGN: A prospective, open-label, one-arm study of 24 weeks duration. PATIENTS AND SETTING: Nineteen patients (18 on stable HAART), with low density lipoprotein (LDL)-cholesterol values of ≥ 130 mg/dl despite the use of pravastatin. METHODS: Ezetimibe, 10 mg/day, was added to pravastatin 20 mg/day, while patients maintained the same antiretroviral regimen. Determinations of total, LDL-, and high density lipoprotein (HDL)-cholesterol, triglycerides, apoproteins, and inflammatory factors (homocystein and C-reactive protein) were performed at baseline, and at weeks 6, 12, and 24. Liver enzymes and creatinine phosphokinase were also assessed. Protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) Cmin was determined just before and 12 weeks after ezetimibe introduction. RESULTS: At week 24, 61.5% of patients achieved the endpoint of the study (LDL-cholesterol < 130 mg/dl). Significant declines in mean total and LDL-cholesterol levels were observed between baseline and weeks 6, 12, and 24, irrespective of antiretroviral type (PI or NNRTI). Mean HDL-cholesterol and apoprotein A increased significantly. No patients discontinued therapy due to intolerance or presented toxicity of grade 2 or more. No differences were observed in lopinavir or nevirapine Cmin measured just before and 12 weeks after ezetimibe introduction. CONCLUSION: The addition of ezetimibe to ongoing pravastatin seems to be an effective and safe option for HIV-infected patients not achieving the NCEP ATPIII LDL-cholesterol goals while receiving a statin alone. Its high tolerability and the lack of interactions with the cytochrome CYP3A4 indicate that ezetimibe will not increase the risk of toxicity or pharmacokinetic interactions with antiretrovirals.

Original languageEnglish (US)
Pages (from-to)2159-2164
Number of pages6
JournalAIDS
Volume20
Issue number17
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Dyslipidemias
Pravastatin
HIV
Lipids
LDL Cholesterol
Apoproteins
Reverse Transcriptase Inhibitors
Protease Inhibitors
HDL Cholesterol
Therapeutics
Pharmacokinetics
Lopinavir
Nevirapine
Cytochrome P-450 CYP3A
Highly Active Antiretroviral Therapy
Cytochromes
LDL Lipoproteins
C-Reactive Protein
Ezetimibe

Keywords

  • Antiretroviral therapy
  • Dyslipidaemia
  • Ezetimibe
  • HIV-infection
  • Pharmacokinetic interactions
  • Statins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Ezetimibe, a promising lipid-lowering agent for the treatment of dyslipidaemia in HIV-infected patients with poor response to statins. / Negredo, Eugenia; Moltó, José; Puig, Jordi; Cinquegrana, Denise; Bonjoch, Anna; Pérez-Álvarez, Núria; López-Blázquez, Raquel; Blanco, Asunción; Clotet, Bonaventura; Rey-Joly, Celestino.

In: AIDS, Vol. 20, No. 17, 01.11.2006, p. 2159-2164.

Research output: Contribution to journalArticle

Negredo, E, Moltó, J, Puig, J, Cinquegrana, D, Bonjoch, A, Pérez-Álvarez, N, López-Blázquez, R, Blanco, A, Clotet, B & Rey-Joly, C 2006, 'Ezetimibe, a promising lipid-lowering agent for the treatment of dyslipidaemia in HIV-infected patients with poor response to statins', AIDS, vol. 20, no. 17, pp. 2159-2164. https://doi.org/10.1097/01.aids.0000247573.95880.db
Negredo, Eugenia ; Moltó, José ; Puig, Jordi ; Cinquegrana, Denise ; Bonjoch, Anna ; Pérez-Álvarez, Núria ; López-Blázquez, Raquel ; Blanco, Asunción ; Clotet, Bonaventura ; Rey-Joly, Celestino. / Ezetimibe, a promising lipid-lowering agent for the treatment of dyslipidaemia in HIV-infected patients with poor response to statins. In: AIDS. 2006 ; Vol. 20, No. 17. pp. 2159-2164.
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abstract = "OBJECTIVE: To assess the efficacy, safety, and pharmacokinetic interactions of ezetimibe in HIV-infected patients with poorly controlled antiretroviral-associated dyslipidaemia while taking pravastatin alone. DESIGN: A prospective, open-label, one-arm study of 24 weeks duration. PATIENTS AND SETTING: Nineteen patients (18 on stable HAART), with low density lipoprotein (LDL)-cholesterol values of ≥ 130 mg/dl despite the use of pravastatin. METHODS: Ezetimibe, 10 mg/day, was added to pravastatin 20 mg/day, while patients maintained the same antiretroviral regimen. Determinations of total, LDL-, and high density lipoprotein (HDL)-cholesterol, triglycerides, apoproteins, and inflammatory factors (homocystein and C-reactive protein) were performed at baseline, and at weeks 6, 12, and 24. Liver enzymes and creatinine phosphokinase were also assessed. Protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) Cmin was determined just before and 12 weeks after ezetimibe introduction. RESULTS: At week 24, 61.5{\%} of patients achieved the endpoint of the study (LDL-cholesterol < 130 mg/dl). Significant declines in mean total and LDL-cholesterol levels were observed between baseline and weeks 6, 12, and 24, irrespective of antiretroviral type (PI or NNRTI). Mean HDL-cholesterol and apoprotein A increased significantly. No patients discontinued therapy due to intolerance or presented toxicity of grade 2 or more. No differences were observed in lopinavir or nevirapine Cmin measured just before and 12 weeks after ezetimibe introduction. CONCLUSION: The addition of ezetimibe to ongoing pravastatin seems to be an effective and safe option for HIV-infected patients not achieving the NCEP ATPIII LDL-cholesterol goals while receiving a statin alone. Its high tolerability and the lack of interactions with the cytochrome CYP3A4 indicate that ezetimibe will not increase the risk of toxicity or pharmacokinetic interactions with antiretrovirals.",
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AU - Negredo, Eugenia

AU - Moltó, José

AU - Puig, Jordi

AU - Cinquegrana, Denise

AU - Bonjoch, Anna

AU - Pérez-Álvarez, Núria

AU - López-Blázquez, Raquel

AU - Blanco, Asunción

AU - Clotet, Bonaventura

AU - Rey-Joly, Celestino

PY - 2006/11/1

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N2 - OBJECTIVE: To assess the efficacy, safety, and pharmacokinetic interactions of ezetimibe in HIV-infected patients with poorly controlled antiretroviral-associated dyslipidaemia while taking pravastatin alone. DESIGN: A prospective, open-label, one-arm study of 24 weeks duration. PATIENTS AND SETTING: Nineteen patients (18 on stable HAART), with low density lipoprotein (LDL)-cholesterol values of ≥ 130 mg/dl despite the use of pravastatin. METHODS: Ezetimibe, 10 mg/day, was added to pravastatin 20 mg/day, while patients maintained the same antiretroviral regimen. Determinations of total, LDL-, and high density lipoprotein (HDL)-cholesterol, triglycerides, apoproteins, and inflammatory factors (homocystein and C-reactive protein) were performed at baseline, and at weeks 6, 12, and 24. Liver enzymes and creatinine phosphokinase were also assessed. Protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) Cmin was determined just before and 12 weeks after ezetimibe introduction. RESULTS: At week 24, 61.5% of patients achieved the endpoint of the study (LDL-cholesterol < 130 mg/dl). Significant declines in mean total and LDL-cholesterol levels were observed between baseline and weeks 6, 12, and 24, irrespective of antiretroviral type (PI or NNRTI). Mean HDL-cholesterol and apoprotein A increased significantly. No patients discontinued therapy due to intolerance or presented toxicity of grade 2 or more. No differences were observed in lopinavir or nevirapine Cmin measured just before and 12 weeks after ezetimibe introduction. CONCLUSION: The addition of ezetimibe to ongoing pravastatin seems to be an effective and safe option for HIV-infected patients not achieving the NCEP ATPIII LDL-cholesterol goals while receiving a statin alone. Its high tolerability and the lack of interactions with the cytochrome CYP3A4 indicate that ezetimibe will not increase the risk of toxicity or pharmacokinetic interactions with antiretrovirals.

AB - OBJECTIVE: To assess the efficacy, safety, and pharmacokinetic interactions of ezetimibe in HIV-infected patients with poorly controlled antiretroviral-associated dyslipidaemia while taking pravastatin alone. DESIGN: A prospective, open-label, one-arm study of 24 weeks duration. PATIENTS AND SETTING: Nineteen patients (18 on stable HAART), with low density lipoprotein (LDL)-cholesterol values of ≥ 130 mg/dl despite the use of pravastatin. METHODS: Ezetimibe, 10 mg/day, was added to pravastatin 20 mg/day, while patients maintained the same antiretroviral regimen. Determinations of total, LDL-, and high density lipoprotein (HDL)-cholesterol, triglycerides, apoproteins, and inflammatory factors (homocystein and C-reactive protein) were performed at baseline, and at weeks 6, 12, and 24. Liver enzymes and creatinine phosphokinase were also assessed. Protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) Cmin was determined just before and 12 weeks after ezetimibe introduction. RESULTS: At week 24, 61.5% of patients achieved the endpoint of the study (LDL-cholesterol < 130 mg/dl). Significant declines in mean total and LDL-cholesterol levels were observed between baseline and weeks 6, 12, and 24, irrespective of antiretroviral type (PI or NNRTI). Mean HDL-cholesterol and apoprotein A increased significantly. No patients discontinued therapy due to intolerance or presented toxicity of grade 2 or more. No differences were observed in lopinavir or nevirapine Cmin measured just before and 12 weeks after ezetimibe introduction. CONCLUSION: The addition of ezetimibe to ongoing pravastatin seems to be an effective and safe option for HIV-infected patients not achieving the NCEP ATPIII LDL-cholesterol goals while receiving a statin alone. Its high tolerability and the lack of interactions with the cytochrome CYP3A4 indicate that ezetimibe will not increase the risk of toxicity or pharmacokinetic interactions with antiretrovirals.

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KW - Dyslipidaemia

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KW - HIV-infection

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