Changes in cardiovascular biomarkers in HIV-infected patients switching from ritonavir-boosted protease inhibitors to raltegravir

Background: Switching from boosted protease inhibitors (PI/r) to raltegravir (RAL) results in a better plasma lipid profile than continuing PI/r. Whether this strategy affects plasma biomarkers associated with atherosclerosis is unknown. Methods: We assessed 48-week changes in fasting lipids and several biomarkers including serum high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein 1 (MCP-1), osteoprotegerin, interleukin (IL) 6, IL-10, tumor necrosis factor alpha (TNF-alpha), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and P-selectin, adiponectin, insulin, and D-dimer in otherwise healthy, virologically suppressed HIV-infected patients treated with PI/r who randomly switched from PI/r to RAL or continued with PI/r in the SPIRAL trial. Biomarkers and lipids at baseline and 48-week changes between both study arms were compared. Correlations between changes in biomarkers and changes in lipids were also evaluated. Results: Of 273 patients initiating study drugs in the SPIRAL trial, 233 (119 RAL, 114 PI/r) remained on allocated therapy for 48 weeks and had sera available for the purpose of this substudy. Triglycerides (-28%, P<0.0001), total (-14%, P<0.0001), low-density lipoprotein (-9%, P=0.0069), and high-density lipoprotein (-10%, P= 0.0017) cholesterol decreased in RAL relative to the PI/r group. Among biomarkers, hsCRP (-40%, P<0.0001), MCP-1 (-20%, P=0.0003), osteoprotegerin (-13%, P= 0.0024), IL-6 (-46%, P<0.0001), TNF-alpha (-27%, P=0.0011), insulin (-26%, P< 0.0001), and D-dimer (-8%, P=0.0187) decreased in RAL relative to PI/r group, whereas IL-10 (+1%, P=0.7773), ICAM-1 (-6%, P=0.1255), VCAM-1(0%, P=0.8671), E-selectin (-9%, P=0.2174), P-selectin (-6%, P=0.3865), and adiponectin (+8%, P=0.2028) remained unchanged. Biomarkers and lipids changes at 48 weeks were weakly correlated. Conclusion: Switching from PI/r to RAL induced significant changes in several cardio-vascular biomarkers that were not completely explained by lipid changes. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins