Statin Therapy to Improve Atherosclerosis in HIV Patients

Study Overview
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Brief Summary
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In HIV patients, statin therapy will attenuate plaque inflammation, thus, making plaques less vulnerable, will deter plaque progression, and improve endothelial function. In addition to known cholesterol-lowering and C-reactive protein lowering effects, immunomodulatory effects of statins will lead to a shift from pro-inflammatory monocyte and T cell subsets to less atherogenic subpopulations.

Official Title
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Statin Therapy to Improve Inflammation and Atherosclerosis in HIV Patients

Conditions
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Cardiovascular Disease, HIV, Atherosclerosis, Inflammation, Statins, HMG-CoA, HIV Infections

Intervention / Treatment
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* Drug: atorvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Men and women age 18-60 with previously diagnosed HIV disease Subclinical coronary artery disease as defined by presence of one or more plaque on coronary CTA without history of cardiac events or cardiac symptoms and no evidence of critical coronary stenosis. Target to background ratio (TBR) as determined by PET of > 1.6. Stable anti-retroviral (ARV) therapy as defined by no changes in ARV regimen for >6 months LDL-cholesterol >70 mg/dL and <130 mg/dL Exclusion criteria: History of acute coronary syndrome Contraindication to statin therapy Current statin use AST or ALT two times greater than the upper limit of normal or receiving treatment for active liver disease Renal disease or creatinine >1.5 mg/dL (given the risk of contrast nephropathy during CT angiography of the heart) Infectious illness within past 3 months Contraindication to beta-blocker (including moderate to severe asthma or heart block) or nitroglycerin use as these drugs are given as part of the standard cardiac CT protocol. Previous allergic reaction to beta blocker or nitroglycerin. Body weight greater than 300 lbs due to CT scanner table limitations Patients with previous allergic reactions to iodine-containing contrast media Active illicit drug use Patients who report any significant radiation exposure over the course of the year prior to randomization. Significant exposure is defined as: More than 2 percutaneous coronary interventions (PCI) within 12 months of randomization More than 2 myocardial perfusion studies within the past 12 months More than 2 CT angiograms within the past 12 months Any subjects with history of radiation therapy. Patients already scheduled or being considered for a procedure or treatment requiring significant radiation exposure (e.g., radiation therapy, PCI, or catheter ablation of arrhythmia) within 12 months of randomization Pregnancy or breastfeeding Coronary artery luminal narrowing >70% seen on coronary CTA

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br>20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months. | Drug: atorvastatin<br>* 20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.<br>|
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coronary and Aortic Plaque Inflammation | 12 month change in mean FDG-PET TBR (18-fluorodeoxyglucose positron emission tomography target-to-background ratio) | Measured at baseline and 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plaque Progression | 12 month percent change in plaque volume | Measured at baseline and 1 year | 
| Endothelial Function | Assessment of endothelial function was to be measured by endothelial vasodilator function. | 1 year | 
| Immune Function | 12 month change in CD4 T-lymphocytes | Measured at baseline and 1 year | 
| Lipid Profile | 12 month change in lipid profile | Measured at baseline and 1 year | 
| C-reactive Protein (CRP) | 12 month change in Log CRP concentration | Measured at baseline and 1 year | 
| Adipocytokines | 12 month change in IL-6 | Measured at baseline and 1 year | 
| Liver Function Tests (LFTs) | Number of participants with LFT abnormalities (greater than or equal to 3 times the upper limit of normal). For reference, the normal ranges for AST and ALT are shown below. Please note that the normal range for ALT at Labcorp changed over the course of the study. AST and ALT elevations were determined based on the normal range at the time the lab test was performed. ALT: 0-40 IU/L, 0-44 IU/L, or 0-55 IU/L AST: 0-40 IU/L | Measured at baseline, 1, 3, 6, 9, and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Cardiovascular Disease, Atherosclerosis, Inflammation, Statins, treatment experienced