BMC Infectious Diseases | |
Evaluation of cardiovascular biomarkers In HIV-infected patients switching to abacavir or tenofovir based therapy | |
Alex L Laursen1  Lars Østergaard1  Bente L Langdahl3  Ulla S Nielsen1  Christian A Frederiksen2  Jesper Melchjorsen1  Martin Tolstrup1  Thomas A Rasmussen1  | |
[1] Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark;Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Skejby, Denmark;Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Skejby, Denmark | |
关键词: cardiovascular disease; tenofovir; abacavir; HIV; | |
Others : 1175582 DOI : 10.1186/1471-2334-11-267 |
|
received in 2011-06-20, accepted in 2011-10-04, 发布年份 2011 | |
【 摘 要 】
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.
【 授权许可】
2011 Rasmussen et al; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150428035312186.pdf | 310KB | download | |
Figure 3. | 20KB | Image | download |
Figure 2. | 68KB | Image | download |
Figure 1. | 47KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, Dabis F, De WS, Law M, D'Arminio MA, Friis-Moller N, Kirk O, Pradier C, Weller I, Phillips AN, Lundgren JD: Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet 2008, 371(9622):1417-1426.
- [2]Ribaudo HJ, Benson CA, Zheng Y, Koletar SL, Collier AC, Lok JJ, Smurzynski M, Bosch RJ, Bastow B, Schouten JT: No risk of myocardial infarction associated with initial antiretroviral treatment containing abacavir: short and long-term results from ACTG A5001/ALLRT. Clin Infect Dis 2011, 52(7):929-940.
- [3]Bedimo RJ, Westfall AO, Drechsler H, Vidiella G, Tebas P: Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era. Clin Infect Dis 2011, 53(1):84-91.
- [4]Obel N, Farkas DK, Kronborg G, Larsen CS, Pedersen G, Riis A, Pedersen C, Gerstoft J, Sorensen HT: Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: a population-based nationwide cohort study. HIVMed 2010, 11(2):130-136.
- [5]Lang S, Mary-Krause M, Cotte L, Gilquin J, Partisani M, Simon A, Boccara F, Costagliola D: Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus-infected patients: a case-control study nested within the French Hospital Database on HIV ANRS cohort CO4. Arch Intern Med 2010, 170(14):1228-1238.
- [6]Brothers CH, Hernandez JE, Cutrell AG, Curtis L, Ait-Khaled M, Bowlin SJ, Hughes SH, Yeo JM, Lapierre DH: Risk of myocardial infarction and abacavir therapy: no increased risk across 52 GlaxoSmithKline-sponsored clinical trials in adult subjects. JAcquirImmuneDeficSyndr 2009, 51(1):20-28.
- [7]Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients AIDS 2008, 22(14):F17-F24.
- [8]Martin A, Bloch M, Amin J, Baker D, Cooper DA, Emery S, Carr A: Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-Lamivudine: a randomized, 96-week trial. ClinInfectDis 2009, 49(10):1591-1601.
- [9]Martinez E, Arranz JA, Podzamczer D, Lonca M, Sanz J, Barragan P, Ribera E, Knobel H, Roca V, Gutierrez F, Blanco JL, Mallolas J, Llibre JM, Clotet B, Dalmau D, Segura F, Arribas JR, Cosin J, Barrufet P, Casas E, Ferrer E, Curran A, Gonzalez A, Pich J, Cruceta A, Arnaiz JA, Miro JM, Gatell JM: A simplification trial switching from nucleoside reverse transcriptase inhibitors to once-daily fixed-dose abacavir/lamivudine or tenofovir/emtricitabine in HIV-1-infected patients with virological suppression. JAcquirImmuneDeficSyndr 2009, 51(3):290-297.
- [10]Sax PE, Tierney C, Collier AC, Fischl MA, Mollan K, Peeples L, Godfrey C, Jahed NC, Myers L, Katzenstein D, Farajallah A, Rooney JF, Ha B, Woodward WC, Koletar SL, Johnson VA, Geiseler PJ, Daar ES: Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. NEnglJMed 2009, 361(23):2230-2240.
- [11]Smith KY, Patel P, Fine D, Bellos N, Sloan L, Lackey P, Kumar PN, Sutherland-Phillips DH, Vavro C, Yau L, Wannamaker P, Shaefer MS: Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment. AIDS 2009, 23(12):1547-1556.
- [12]Ding A-CEX, Cooper C, Miele P, Kornegay C, Soukup M, Marcus K: No Association of Myocardial Infarction with Abacavir Use. In 18th Conference on Retroviruses and Opportunistic Infections. Boston; 2011. Abstract # O-1004
- [13]Danesh J, Kaptoge S, Mann AG, Sarwar N, Wood A, Angleman SB, Wensley F, Higgins JP, Lennon L, Eiriksdottir G, Rumley A, Whincup PH, Lowe GD, Gudnason V: Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoSMed 2008, 5(4):e78.
- [14]Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GD, Pepys MB, Gudnason V: C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. NEnglJMed 2004, 350(14):1387-1397.
- [15]Ridker PM, Hennekens CH, Buring JE, Rifai N: C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. NEnglJMed 2000, 342(12):836-843.
- [16]Hammond E, McKinnon E, Mallal S, Nolan D: Longitudinal evaluation of cardiovascular disease-associated biomarkers in relation to abacavir therapy. AIDS 2008, 22(18):2540-2543.
- [17]Jong E, Meijers JC, van Gorp EC, Spek CA, Mulder JW: Markers of inflammation and coagulation indicate a prothrombotic state in HIV-infected patients with long-term use of antiretroviral therapy with or without abacavir. AIDS ResTher 2010, 7:9.
- [18]Martinez E, Larrousse M, Podzamczer D, Perez I, Gutierrez F, Lonca M, Barragan P, Deulofeu R, Casamitjana R, Mallolas J, Pich J, Gatell JM: Abacavir-based therapy does not affect biological mechanisms associated with cardiovascular dysfunction. AIDS 2010, 24(3):F1-F9.
- [19]Kristoffersen US, Kofoed K, Kronborg G, Benfield T, Kjaer A, Lebech AM: Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV-1-infected individuals receiving combination antiretroviral therapy. HIVMed 2009, 10(10):627-633.
- [20]Humphries A, Amin J, Cooper D, Carr A, Kelleher A, Bloch M: Changes in Cardiovascular Biomarkers with Abacavir: A Randomized, 96-week trial. In Paper #718, 17th Conference on Retroviruses and Oppertunistic Infections. San Francisco, USA; 2010.
- [21]Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB: Prediction of coronary heart disease using risk factor categories. Circulation 1998, 97(18):1837-1847.
- [22]Pearson TA, Bazzarre TL, Daniels SR, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, Hong Y, Mensah GA, Sallis JF, Smith S, Stone NJ, Taubert KA: American Heart Association guide for improving cardiovascular health at the community level: a statement for public health practitioners, healthcare providers, and health policy makers from the American Heart Association Expert Panel on Population and Prevention Science. Circulation 2003, 107(4):645-651.
- [23]Sabatine MS, Morrow DA, Jablonski KA, Rice MM, Warnica JW, Domanski MJ, Hsia J, Gersh BJ, Rifai N, Ridker PM, Pfeffer MA, Braunwald E: Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation 2007, 115(12):1528-1536.
- [24]Padilla S, Masia M, Garcia N, Jarrin I, Tormo C, Gutierrez F: Early changes in inflammatory and pro-thrombotic biomarkers in patients initiating antiretroviral therapy with abacavir or tenofovir. BMC Infect Dis 2011, 11(1):40. BioMed Central Full Text
- [25]De PC, Orden S, Apostolova N, Blanquer A, Esplugues JV, Alvarez A: Abacavir and didanosine induce the interaction between human leukocytes and endothelial cells through Mac-1 upregulation. AIDS 2010, 24(9):1259-1266.
- [26]Mulvihill NT, Foley JB, Murphy R, Crean P, Walsh M: Evidence of prolonged inflammation in unstable angina and non-Q wave myocardial infarction. JAmCollCardiol 2000, 36(4):1210-1216.
- [27]Blankenberg S, Rupprecht HJ, Bickel C, Peetz D, Hafner G, Tiret L, Meyer J: Circulating cell adhesion molecules and death in patients with coronary artery disease. Circulation 2001, 104(12):1336-1342.
- [28]Blankenberg S, Barbaux S, Tiret L: Adhesion molecules and atherosclerosis. Atherosclerosis 2003, 170(2):191-203.
- [29]Hwang SJ, Ballantyne CM, Sharrett AR, Smith LC, Davis CE, Gotto AM, Boerwinkle E: Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities (ARIC) study. Circulation 1997, 96(12):4219-4225.
- [30]Melchjorsen J, Risor MW, Sogaard OS, O'Loughlin K L, Chow S, Paludan SR, Ellermann-Eriksen S, Hedley DW, Phd HM, Ostergaard L, Phd MT: Tenofovir selectively regulates production of inflammatory cytokines and shifts the IL-12/IL-10 balance in human primary cells. J Acquir Immune Defic Syndr 2011.