title: Changes in cardiovascular biomarkers in HIV-infected patients switching from ritonavir-boosted protease inhibitors to raltegravir.
abstract: 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-α), 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-α (-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.
  
  
  CONCLUSIONS
  : Switching from PI/r to RAL induced significant changes in several cardiovascular biomarkers that were not completely explained by lipid changes.
authors.affiliation: Hospital Clínic-IDIBAPS, Universitat de Barcelona, Spain. esteban@fundsoriano.es
authors.forename: Esteban
authors.initials: E
authors.lastname: Martínez
authors.forename: Polyana M
authors.initials: PM
authors.lastname: D'Albuquerque
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
authors.forename: Felix
authors.initials: F
authors.lastname: Gutierrez
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
authors.forename: Antonio
authors.initials: A
authors.lastname: Antela
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Xabier
authors.initials: X
authors.lastname: Moreno
authors.forename: Ignacio
authors.initials: I
authors.lastname: Perez
authors.forename: Judit
authors.initials: J
authors.lastname: Pich
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D050197:Atherosclerosis / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D004334:Drug Administration Schedule; D019040:E-Selectin / Q000378:metabolism; D005215:Fasting; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood; D019007:P-Selectin / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology*; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019040:E-Selectin; D017320:HIV Protease Inhibitors; D015850:Interleukin-6; D008055:Lipids; D053244:Osteoprotegerin; D019007:P-Selectin; D011760:Pyrrolidinones; C506030:TNFRSF11B protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D016753:Interleukin-10; D000068898:Raltegravir Potassium; D002097:C-Reactive Protein; D019438:Ritonavir