Markers of inflammation and coagulation indicate a prothrombotic state in HIV-infected patients with long-term use of antiretroviral therapy with or without abacavir.
BACKGROUND
Abacavir (ABC) treatment has been associated with an increased incidence of myocardial infarction. The pathophysiological mechanism is unknown. In this study markers of inflammation and coagulation in HIV-infected patients using antiretroviral therapy with or without ABC were examined to pinpoint a pathogenic mechanism. Given the important role of high sensitivity C-reactive protein (hsCRP) levels in predicting cardiovascular risk, patient groups were also analyzed according to hsCRP levels.


METHODS
Patients treated with ABC and a matched control group treated without ABC were selected retrospectively. Vascular endothelial growth factor (VEGF) and markers of endothelial cell activation (von Willebrand factor (vWF), factor VIII), fibrin formation (fibrinogen, D-dimer, prothrombin fragment 1+2 (F1+2), endogenous thrombin potential (ETP)), anticoagulation markers (protein C and S, activated protein C sensitivity ratio (APCsr)) and inflammation markers (IL-6, hsCRP) were measured in citrated plasma.


RESULTS
A total of 81 patients were included of whom 27 patients used an ABC-containing regimen and 54 used a non-ABC-containing regimen. Patient characteristics were not significantly different between the groups except for longer duration of use of the current antiretroviral regimen in the ABC group (p = 0.01). The median time on ABC was 68 months (interquartile range 59-80 months). No differences in coagulation and inflammation markers according to ABC use were observed. For the whole patient group elevated vWF and F1+2 levels were observed in 23% and 37%, respectively. Compared to the reference ranges for the general population increased APCsr was found in 79% and lower protein C and VEGF levels in 40% and 43%, respectively. Patients in the high-risk category for cardiovascular disease with hsCRP levels > 3 mg/L had significantly higher fibrinogen, D-dimer, F1+2 and ETP levels compared to patients from the low-risk category with hsCRP levels < 1 mg/L.


CONCLUSIONS
HIV-infected patients using ABC showed no specific abnormalities in coagulation or inflammation markers that might explain the increased risk of myocardial infarction. For the whole group, regardless of ABC use, evidence of a prothrombotic state was observed. Thirty-three percent of patients with long-term use of antiretroviral treatment had hsCRP levels above 3 mg/L, which is strongly associated with cardiovascular disease in HIV-uninfected individuals.
Jong
Eefje
E
Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands. eefje.jong@slz.nl
Meijers
Joost C M
JC
van Gorp
Eric C M
EC
Spek
C Arnold
CA
Mulder
Jan W
JW
AIDS Patient Care STDS. 2009 Dec;23(12):1001-7
19929230
HIV Med. 2010 Feb;11(2):130-6
19682101
Thromb Haemost. 2008 Aug;100(2):240-5
18690343
N Engl J Med. 2008 Mar 13;358(11):1129-36
18337603
J Acquir Immune Defic Syndr. 2009 May 1;51(1):20-8
19282778
Nat Med. 2002 Mar;8(3):225-32
11875492
Am J Med. 2004 Mar 22;116 Suppl 6A:9S-16S
15050187
Lancet. 2008 Apr 26;371(9622):1417-26
18387667
HIV Med. 2009 Nov;10(10):627-33
19891054
Neoplasia. 2006 Nov;8(11):889-95
17132220
AIDS. 2009 Sep 24;23(15):2021-7
19542863
AIDS. 2008 Sep 12;22(14):F17-24
18753925