title: Evaluation of cardiovascular biomarkers in HIV-infected patients switching to abacavir or tenofovir based therapy.
abstract: BACKGROUND
  Our objective was to evaluate and compare the effect of abacavir on levels of biomarkers associated with cardiovascular risk.
  
  
  METHODS
  In an open-label randomized trial, HIV-infected patients were randomized 1:1 to switch from zidovudine/lamivudine to abacavir/lamivudine or tenofovir/emtricitabine. In the present analysis, we measured levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), E-selectin, and myeloperoxidase (MPO) at baseline and 4, 12, and 48 weeks after randomization. D-dimer and fasting lipids were measured at baseline and weeks 12 and 48. Levels of biomarkers at all time points and changes from baseline were compared across study arms using Wilcoxon rank sum test.
  
  
  RESULTS
  Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. Levels of E-selectin (P=0.004) and sVCAM-1 (P=0.041) increased transiently from baseline to week 4 in the abacavir arm compared with the tenofovir arm, but no long-term increases were detected. We found no significant differences between study arms in the levels or changes in the levels of sICAM-1, MPO, d-dimer, IL-6, or hs-CRP. Levels of total cholesterol and high density lipoprotein (HDL) increased in the abacavir arm relative to the tenofovir arm, but no difference was found in total cholesterol/HDL ratio.
  
  
  CONCLUSIONS
  In patients randomized to abacavir-based HIV-treatment transient increases were seen in the plasma levels of E-selectin and sVCAM-1 compared with treatment with tenofovir, but no difference between study arms was found in other biomarkers associated with endothelial dysfunction, inflammation, or coagulation. The clinical significance of these findings is uncertain. TRIAL REGESTRATION: Clinicaltrials.gov identifier: NCT00647244.
authors.affiliation: Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark. thomrasm@rm.dk
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rasmussen
authors.forename: Martin
authors.initials: M
authors.lastname: Tolstrup
authors.forename: Jesper
authors.initials: J
authors.lastname: Melchjorsen
authors.forename: Christian A
authors.initials: CA
authors.lastname: Frederiksen
authors.forename: Ulla S
authors.initials: US
authors.lastname: Nielsen
authors.forename: Bente L
authors.initials: BL
authors.lastname: Langdahl
authors.forename: Lars
authors.initials: L
authors.lastname: Østergaard
authors.forename: Alex L
authors.initials: AL
authors.lastname: Laursen
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015224:Dideoxynucleosides / Q000008:administration & dosage*; D019040:E-Selectin / Q000097:blood; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage*; D010949:Plasma / Q000737:chemistry; D000068698:Tenofovir; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D000099227:Abacavir
chemical_list: D000225:Adenine; D019380:Anti-HIV Agents; D015415:Biomarkers; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D019040:E-Selectin; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D000068698:Tenofovir; D019010:Vascular Cell Adhesion Molecule-1; D000099227:Abacavir