Cardiovascular Disease, Glucose Metabolism, HIV Infections, Lipid Metabolism, Lipodystrophy, Metabolic Abnormality
Conditions
Keywords
Hyperlipidaemia, Lipid metabolism, Glucose metabolism, HMG CoA reductase inhibitors, Lipodystrophy, Cardiovascular disease, Treatment Experienced, HIV
Brief summary
This study is a randomised, placebo-controlled study of the effect of treatment with the HMG-CoA reductase inhibitor, pravastatin, in HIV-infected, protease inhibitor treated patients with high serum cholesterol. We hypothesise that pravastatin will result in greater reductions in cholesterol than placebo when used in conjunction with appropriate dietary advice.
Detailed description
High serum cholesterol concentrations are commonly seen in HIV-infected patients treated with some protease inhibitor medications as part of long-term antiretroviral therapy for HIV. There is concern that these elevations in cholesterol may negatively impact on long-term risk of cardiovascular disease in this patient population. Pravastatin, a HMG-CoA reductase inhibitor, is commonly used to treat hypercholesterolaemia in the general population. We aim to examine the effect of 12 weeks therapy with 40mg pravastatin daily in conjunction with dietary advice in HIV-infected patients with elevated serum cholesterol on continued protease inhibitor therapy. After 4 weeks of dietary advice, patients will be randomised to receive either pravastatin or placebo for 12 weeks. Assessments include fasting lipid and glycaemic parameters, measures of body composition and HIV disease, and surrogate markers for cardiovascular disease. Although previous small studies of pravastatin in this field have been performed, none has done so in a randomised placebo controlled trial taking into account all the relevant measures.
Interventions
DRUGPravastatin
Sponsors
The University of New South Wales
National Heart, Lung, and Blood Institute (NHLBI)
Garvan Institute of Medical Research
St Vincent's Hospital, Sydney
Kirby Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provide written informed consent to participate in the trial * HIV-1 sero-positive * Male/female \>18 years age * Currently receiving HIV protease inhibitor therapy for \> 12 weeks and unlikely to require change in existing regimen during the 16 week study period * Fasting cholesterol \> 6.5 mmol/L (mean of 2 samples collected \> 3 days apart)
Exclusion criteria
* Any condition which may interfere with ability to comply with study * Gastrointestinal disorder which may affect drug absorption * Hypertension or congestive cardiac failure * Lactic acidemia (serum lactate level \>2.2 mmol/L) * Any serious medical condition which may compromise the patient's safety, including pancreatitis or hepatitis within past 6 months * Active AIDS defining conditions * Concurrent therapy with any other lipid lowering agents, oral hypoglycaemics, anabolic steroids or insulin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Between-group difference in time weighted change from baseline in fasting serum total cholesterol | — |
Secondary
| Measure | Time frame |
|---|---|
| Includes: between-group difference in time weighted change: from wk 4 in fasting serum total cholesterol as well as from baseline in HDL-cholesterol and triglycerides; in total and regional body fat; in endothelial function | — |
Countries
Australia
Outcome results
None listed