VHRM_5206_De Lorenzo.indd

Correspondence: Ferruccio De Lorenzo Consultant Physician, General Medicine and Prevention of Vascular Disorders, Beta Cell Diabetes Centre and St Stephen’s AIDS Trust, Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK Email [email protected] Investigational 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) infl ammatory 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/mm. 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 infl ammatory 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 fi rst time, this study will investigate anti-infl ammatory and anti-atherogenic effects of a pharmacological lipid-lowering agent in HIV-IP that may lead to the reduction of CVD.