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 > or = 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.
OBJECTIVE: To assess the efficacy, safety, and pharmacokinetic interactions of ezetimibe in HIV-infectedpatients 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 > or = 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-infectedpatients 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.
Authors: S Oswald; H E Meyer zu Schwabedissen; A Nassif; C Modess; Z Desta; E T Ogburn; J Mostertz; M Keiser; J Jia; A Hubeny; A Ulrich; D Runge; M Marinova; D Lütjohann; H K Kroemer; W Siegmund Journal: Clin Pharmacol Ther Date: 2012-02-01 Impact factor: 6.875
Authors: Dominic Chow; Huichao Chen; Marshall J Glesby; Anthony Busti; Scott Souza; Janet Andersen; Sharon Kohrs; Julia Wu; Susan L Koletar Journal: AIDS Date: 2009-10-23 Impact factor: 4.177