title: Effects of abacavir administration on structural and functional markers of platelet activation.
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].
  
  
  CONCLUSIONS
  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.
authors.affiliation: aDepartment of Infectious Diseases, Alfred Hospital bDepartment of Infectious Diseases, Faculty of Medicine, Nursing and Health Sciences, cAustralian Centre for Bloods Diseases, Monash University, Melbourne, Australia.
authors.forename: Janine M
authors.initials: JM
authors.lastname: Trevillyan
authors.forename: Jane F
authors.initials: JF
authors.lastname: Arthur
authors.forename: Jing
authors.initials: J
authors.lastname: Jing
authors.forename: Robert K
authors.initials: RK
authors.lastname: Andrews
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Gardiner
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Hoy
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D015224:Dideoxynucleosides / Q000008:administration & dosage* / Q000009:adverse effects*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D000099227:Abacavir