Prevention of atherosclerosis in patients living with HIV.
INVESTIGATIONAL PRODUCT: Rosuvastatin (Crestor; Astra Zeneca).
Rosuvastatin (5 mg).
Prevention of Atherosclerosis in Patients Living with HIV.
Phase III.


OBJECTIVE
PRIMARY AIM: To assess whether rosuvastatin therapy could slow the progression of the carotid intima-media thickness (C-IMT; as measured by the change in the mean IMT of the near and far walls of the distal common carotid arteries) over 2 years in HIV-infected patients (HIV-IP).
To assess whether rosuvastatin therapy could reduce highly sensitive C reactive protein (hs-CRP) inflammatory marker that is increased in HIV-IP.To assess the effect of rosuvastatin therapy on serum lipid levels (total cholesterol [TC], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and apolipoproteins (APO A1, APO B and APO B/A1).To assess the safety of rosuvastatin in HIV-IP through the evaluation of clinical laboratory analyses (liver function tests and creatine kinase) and adverse events (AEs).


METHODS
Two-year randomized, double-blind, placebo-controlled, parallel group study.
320 HIV-IP.
HIV-IP who are aged between 30 and 60 years, with a CD4 count. greater than 200 cells/mm(3). Patients must be stable on combination antiretroviral therapy (cART) for at least 12 months and have a 10-year CVD risk of less than 20% (using the Framingham risk score).
One.
Two years (5 mg rosuvastatin or placebo once daily).
Oral rosuvastatin (5 mg) once daily. The incidence of cardiovascular disease (CVD) in HIV-IP is at least three times higher than in the general population and further increases each year with combination anti-retroviral therapy (cART). The carotid atherosclerosis progression rate is 10 times higher in HIV-IP than in uninfected individuals. The aim of this study is to assess whether therapy with 5 mg rosuvastatin could: 1) Slow the progression in the mean IMT of the distal common carotid arteries over two years in HIV-IP.2) Change the concentration in the inflammatory marker--hs-CRP, which is increased in HIV-IP.3) Change the concentrations of TC, LDL cholesterol, HDL cholesterol, TG, apolipoproteins (APO) B, APO A1 and APO B/A1.4) Be administered safely in the study population. Pharmacological intervention with rosuvastatin will be evaluated in a double-blind, placebo-controlled, randomized clinical trial in HIV-IP treated with cART not matching the published selection criteria for lipid-lowering therapy. For the first time, this study will investigate anti-inflammatory and anti-atherogenic effects of a pharmacological lipid-lowering agent in HIV-IP that may lead to the reduction of CVD.
De Lorenzo
Ferruccio
F
General Medicine and Prevention of Vascular Disorders, Beta Cell Diabetes Centre and St Stephen's AIDS Trust, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK. fdlx@btinternet.com
Boffito
Marta
M
Collot-Teixeira
Sophie
S
Gazzard
Brian
B
McGregor
John L
JL
Shotliff
Kevin
K
Xiao
Han
H
D000284:Administration, Oral; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000097:blood / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D018450:Disease Progression; D004311:Double-Blind Method; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein