TY - JOUR
T1 - Evaluation of cardiovascular biomarkers in HIV-infected patients switching to abacavir or tenofovir based therapy
AU - Rasmussen, Thomas A
AU - Tolstrup, Martin
AU - Melchjorsen, Jesper
AU - Frederiksen, Christian A
AU - Nielsen, Ulla S
AU - Langdahl, Bente L
AU - Østergaard, Lars
AU - Laursen, Alex L
PY - 2011/10/4
Y1 - 2011/10/4
N2 - 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.CONCLUSION: 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.
AB - 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.CONCLUSION: 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.
KW - Adenine/administration & dosage
KW - Adult
KW - Anti-HIV Agents/administration & dosage
KW - Antiretroviral Therapy, Highly Active/methods
KW - Biomarkers/blood
KW - Cardiovascular Diseases/physiopathology
KW - Deoxycytidine/administration & dosage
KW - Dideoxynucleosides/administration & dosage
KW - E-Selectin/blood
KW - Emtricitabine
KW - Female
KW - HIV Infections/drug therapy
KW - Humans
KW - Lamivudine/administration & dosage
KW - Male
KW - Middle Aged
KW - Organophosphonates/administration & dosage
KW - Plasma/chemistry
KW - Tenofovir
KW - Vascular Cell Adhesion Molecule-1/blood
U2 - 10.1186/1471-2334-11-267
DO - 10.1186/1471-2334-11-267
M3 - Journal article
C2 - 21970555
SN - 1471-2334
VL - 11
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
M1 - 267
ER -