Statin Therapy to Improve Atherosclerosis in HIV Patients

This study has been completed.
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Steven K. Grinspoon, MD, Massachusetts General Hospital Identifier:
First received: August 24, 2009
Last updated: February 17, 2015
Last verified: February 2015
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.

Condition Intervention
Cardiovascular Disease
Statins, HMG-CoA
HIV Infections
Drug: atorvastatin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Statin Therapy to Improve Inflammation and Atherosclerosis in HIV Patients

Resource links provided by NLM:

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Coronary and Aortic Plaque Inflammation [ Time Frame: Measured at baseline and 1 year ] [ Designated as safety issue: No ]
    12 month change in mean FDG-PET TBR (18-fluorodeoxyglucose positron emission tomography target-to-background ratio)

Secondary Outcome Measures:
  • Plaque Progression [ Time Frame: Measured at baseline and 1 year ] [ Designated as safety issue: No ]
    12 month percent change in plaque volume

  • Endothelial Function [ Time Frame: Measured at 1 year ] [ Designated as safety issue: No ]
  • Immune Function [ Time Frame: Measured at baseline and 1 year ] [ Designated as safety issue: No ]
    12 month change in CD4 T-lymphocytes

  • Lipid Profile [ Time Frame: Measured at baseline and 1 year ] [ Designated as safety issue: No ]
    12 month change in lipid profile

  • C-reactive Protein (CRP) [ Time Frame: Measured at baseline and 1 year ] [ Designated as safety issue: No ]
    12 month change in Log CRP concentration

  • Adipocytokines [ Time Frame: Measured at 1 year ] [ Designated as safety issue: No ]
  • Liver Function Tests (LFTs) [ Time Frame: Measured at baseline, 1, 3, 6, 9, and 12 months ] [ Designated as safety issue: Yes ]

    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

Enrollment: 40
Study Start Date: September 2009
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvastatin
20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.
Drug: atorvastatin
20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.
Placebo Comparator: placebo Drug: Placebo


Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Men and women age 18-60 with previously diagnosed HIV disease
  2. 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.
  3. Stable anti-retroviral (ARV) therapy as defined by no changes in ARV regimen for >6 months
  4. LDL-cholesterol >70 mg/dL and <130 mg/dL

Exclusion criteria:

  1. History of acute coronary syndrome
  2. Contraindication to statin therapy
  3. Current statin use
  4. AST or ALT two times greater than the upper limit of normal or receiving treatment for active liver disease
  5. Renal disease or creatinine >1.5 mg/dL (given the risk of contrast nephropathy during CT angiography of the heart)
  6. Infectious illness within past 3 months
  7. 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.
  8. Body weight greater than 300 lbs due to CT scanner table limitations
  9. Patients with previous allergic reactions to iodine-containing contrast media
  10. Active illicit drug use
  11. Patients who report any significant radiation exposure over the course of the year prior to randomization. Significant exposure is defined as:

    1. More than 2 percutaneous coronary interventions (PCI) within 12 months of randomization
    2. More than 2 myocardial perfusion studies within the past 12 months
    3. More than 2 CT angiograms within the past 12 months
    4. Any subjects with history of radiation therapy.
  12. 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
  13. Pregnancy or breastfeeding
  14. Coronary artery luminal narrowing >70% seen on coronary CTA
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Please refer to this study by its identifier: NCT00965185

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Steven K. Grinspoon, MD Massachusetts General Hospital
  More Information

Responsible Party: Steven K. Grinspoon, MD, Professor of Medicine, Harvard Medical School, Massachusetts General Hospital Identifier: NCT00965185     History of Changes
Other Study ID Numbers: 2008-P-000257  R01HL095123  HL 095123 
Study First Received: August 24, 2009
Results First Received: January 30, 2015
Last Updated: February 17, 2015
Health Authority: United States: Federal Government

Keywords provided by Massachusetts General Hospital:
Cardiovascular Disease
treatment experienced

Additional relevant MeSH terms:
Cardiovascular Diseases
Arterial Occlusive Diseases
Pathologic Processes
Vascular Diseases
Atorvastatin Calcium
Anticholesteremic Agents
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action processed this record on May 30, 2016