Background:  HIV-infected individuals have accelerated atherosclerosis. This may be due to both HIV disease-associated factors (including inflammation) and treatment-associated factors. Recently, exposure to abacavir (ABC) has been associated with increased risk of cardiovascular events, for reasons that remain to be elucidated. As endothelial dysfunction is central to the pathogenesis of atherosclerosis and predicts adverse cardiovascular outcomes including myocardial infarction, we investigated the association between treatment- and disease-associated factors on endothelial function, focusing on patients responding to HAART.

Methods:  We studied a cohort of 61 HAART-treated patients who had undetectable plasma HIV RNA levels in whom ABC was currently part of the treatment in half of the patients (n = 30, 49%). Endothelial function was assessed as flow-mediated vasodilation of the brachial artery and was measured using a validated approach in our laboratory; all studies were performed by a single technician blinded to treatment status.  We adjusted for traditional risk factors and HIV characteristics (CD4 count, nadir CD4 count, and HAART duration).

Results:  The median age was 50 years (IQR 45 to 57), and 95% were male. The median duration of HIV infection was 18 years (IQR 14 to 21), the median CD4 cell count was 369 cells/mm³ (IQR 189 to 673), and the median duration of HAART was 8.6 years. Overall, the median flow-mediated vasodilation in the HIV patients was impaired (3.5%; IQR 2.3 to 5.6%). The flow-mediated vasodilation was more impaired in the ABC-treated patients than those not on ABC (2.8% vs 4.9%, p = 0.01). After adjustment for age, gender, traditional risk factors, HIV-specific factors, and baseline brachial artery diameter, current ABC use was independently associated with lower flow-mediated vasodilation (p = 0.017). Duration of HAART and protease inhibitors, CD4 nadir, and proximal CD4 count were not associated with reduced flow-mediated vasodilation.  

Conclusions:  Endothelial function, a central mechanism in atherosclerosis and a marker of cardiovascular risk, is impaired among long-term HAART-treated patients with undetectable viral loads. Current use of ABC was independently associated with impaired endothelial function; this effect was not readily explained by measured confounders, including traditional risk factors. Further studies will need to determine whether ABC-associated changes in endothelial function contribute to the clinically observed relationship between ABC use and myocardial infarction.