Effects of abacavir administration on structural and functional markers of platelet activation


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Abstract

Background:Current abacavir exposure has been reported to be associated with cardiovascular disease. Changes in platelet reactivity could plausibly explain the clinically observed pattern of association.Objective:To determine if platelet reactivity changed following abacavir exposure and whether this effect was reversible on cessation of the drug.Methods:In an open-label, interventional study abacavir, 600 mg daily, was added to a suppressive antiretroviral regimen in 20 adult HIV-positive men. Platelet function, estimated by the phosphorylated vasodilator-stimulated phosphoprotein (P-VASP) assay and through measurement of the expression and shedding of platelet-specific receptors, was assessed at baseline, following 15 days of abacavir and at completion of a 28-day washout period.Results:The VASP-index decreased significantly from 79.1% [interquartile range (IQR) 47.8–87.6] to 32.6% (IQR –11.5–51.0) following 15 days of abacavir administration (P = 0.010), and returned to baseline levels following the washout period (day 43 =76.3%; IQR 40.7–92.3). There was no change in resting (prostaglandin E1 alone) P-VASP but a slight increase in P-VASP within stimulated platelets (prostaglandin E1 and adenosine diphosphate). Integrin β3 levels decreased significantly [208.5 ng/ml (IQR 177.0–231.1) to 177.5 ng/ml (IQR 151.7–205) P < 0.001] and there was a nonsignificant trend towards decreased soluble glycoprotein VI levels [baseline; 72.5 ng/ml (95% CI 58.3–81.5) vs. day 15; 45.0 ng/ml (95% CI 33.0–98.2) P = 0.79].Conclusion:Abacavir led to reversible changes in platelet function and structure. The clinical implications of these changes are uncertain; they may represent negative feedback mechanisms in response to an abacavir-associated prothrombotic state.

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