Ferruccio De Lorenzo1, Marta Boffito1, Sophie Collot-Teixeira2, Brian Gazzard1, John L McGregor2,3, Kevin Shotliff2, Han Xiao41General 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; 2Kings College London, Cardiovascular Division, London, UK; 3INSERM U970, PARC Hôpital Européen George Pompidou, Paris, France; 4Cardiology Department, Homerton University Hospital NHS, London, UKInvestigational product: Rosuvastatin (Crestor®; Astra Zeneca).Active ingredients: Rosuvastatin (5 mg).Study title: Prevention of Atherosclerosis in Patients Living with HIV.Phase of study: Phase III.Aims: 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).Secondary aims:• 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).Study design: Two-year randomized, double-blind, placebo-controlled, parallel group study.Planned sample size: 320 HIV-IP.Summary of eligibility criteria: HIV-IP who are aged between 30 and 60 years, with a CD4 count. greater than 200 cells/mm3. 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).Number of study centers: One.Duration of treatment: Two years (5 mg rosuvastatin or placebo once daily).Dose and route of administration: 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.Keywords: rosuvastatin, atherosclerosis, cardiovascular disease, HIV, clinical trial protoco
