Effects of Pitavastatin on Lipid Profiles in HIV-infected Patients With Dyslipidemia and Receiving Atazanavir/Ritonavir

Phase 4

Completed

Brief Summary: Dyslipidemia as a risk factor for cardiovascular disease (CVD) is an increasing problem in HIV-infected patients who are on antiretroviral therapy especially protease inhibitors including atazanavir. Pitavastatin is a new HMG-CoA reductase inhibitor with lesser drug-drug interactions and demonstrable efficacy in decreasing lipid levels in non HIV-infected individuals. The study was conducted as a randomized, double-blind, crossover study comparing the safety and efficacy of pitavastatin versus placebo in HIV-infected patients with dyslipidemia and receiving atazanavir/ritonavir. Patients were randomized to receive either placebo or pitavastatin for 12 weeks, underwent a 2-week washout period, and then were given the other treatment for an additional 12 weeks. Patients were observed for lipid profiles including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL); and the side effects including clinical and laboratory (serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine phosphokinase (CPK)). The follow-up visits were every 4 weeks until the end of the study.

Recruitment & Eligibility

Inclusion Criteria

aged ≥18 years
able to provide informed consent
had confirmed HIV infection
on ART including atazanavir 300 mg and ritonavir 100 mg each day in the regimens that were not changed within 12 weeks before the randomization
patients who had cholesterol level between 200 and 500 and LDL between 130 and 400 mg/dL without any lipid-lowering agent or discontinued the lipid-lowering agent at least 1 month prior to randomization

Exclusion Criteria

had the history of pitavastatin and/or the constituent of the drugs allergy
known history of myocardial infarction and/or ischemic stroke within 1 month prior to the randomization that would be endangered if we stopped the previous lipid-lowering agent before the enrollment
abnormal AST and ALT with level ≥5 times in asymptomatic patients or ≥3 times of upper normal limit (UNL) in symptomatic patients
pregnancy or breastfeeding
on cyclosporine which had major drug interactions with pitavastatin
patients who denied to join the study

Arm && Interventions

Group	Intervention	Description
Treatment sequence A, B	pitavastatin	Treatment visits were seperated by a 2-week washout period. Treatment A = administration pitavastatin for 12 weeks; Treatment B = administration placebo for 12 weeks
Treatment sequence A, B	placebo	Treatment visits were seperated by a 2-week washout period. Treatment A = administration pitavastatin for 12 weeks; Treatment B = administration placebo for 12 weeks
Treatment sequence B, A	pitavastatin	Treatment visits were seperated by a 2-week washout period. Treatment B = adminstration placebo for 12 weeks; Treatment A = adminstration pitavastatin for 12 weeks
Treatment sequence B, A	placebo	Treatment visits were seperated by a 2-week washout period. Treatment B = adminstration placebo for 12 weeks; Treatment A = adminstration pitavastatin for 12 weeks

Primary Outcome Measures

Name	Time	Method
Efficacy of Pitavastatin in HIV-infected Patients With Dyslipidemia and Receiving Atazanavir/Ritonavir	12 weeks	Efficacy was measured by level of TC, TG, LDL, and HDL that decreased after pitavastatin treatment. Pitavastatin was considered efficient when it could decrease TC, TG, LDL, or HDL significantly compared to placebo.

Secondary Outcome Measures

Name	Time	Method
Safety of Pitavastatin in HIV-infected Patients	12 weeks	Safety clinical was defined by FDA; grade 1 mild symptoms; grade 2 moderate symptoms with limiting age-appropriate IADL; grade 3 severe symptoms with limiting self-care ADL, But not immediately life-threatening; grade 4 life-threatening consequences; and grade 5 death related to adverse event. Safety laboratory evaluation was determined safe if AST, ALT, and/or CPK level was not increased significantly comparing pitavastatin to placebo.