Treatment of hypertriglyceridemia and HIV: fenofibrate-induced changes in the expression of chemokine genes in circulating leukocytes

The impact of mutant chemokine ligands and receptors in the host susceptibility to HIV infection, in the clinical course of the disease and in the development of new therapies has been extensively described [1]. Chemokines have also been implicated in the higher rates of atherosclerosis observed in HIV-infected patients which has been partially attributed to either a direct effect of highly active antiretroviral therapies or the concomitant metabolic abnormalities [2-4]. Treatment of HIV infection, particularly with the use of protease inhibitors (PIs), can raise triglyceride levels to the threshold indicated for intervention. Therefore, the need to maintain viral suppression may be challenged by the need to treat abnormal lipid levels. Fibrates, ligands for peroxisome proliferator-activated receptor α (PPARα), represent an effective treatment for hypertriglyceridemia that reduce coronary events and delay progression of coronary atherosclerosis [5,6]. We hypothesized that such a treatment with fenofibrate may change the expression of chemokine genes in tissues and that this effect could be readily observed in circulating leukocytes.Patients included in this cross-sectional study are participants of a previous study and the design has been already described [3]. Participants were selected among those on a PIs regimen and undetectable viral load during the previous 12 months. They were free of liver and renal disease. Forty-three patients were considered normotriglyceridemic and 39 hypertriglyceridemics (plasma values below or above the accepted threshold of 1.69 mmol/L). Fifteen of these hypertriglyceridemic patients were being treated with fenofibrate (160 mg/day) for at least six month, after having fulfilled the eligibility criteria (more than 6 months on stable HAART, more than 18 years of age, and a fasting triglyceride concentration >1.69 mmol/L). We collated pertinent HIV-related clinical and laboratory data as well as data on the course of plasma lipid profil