title: Increased platelet reactivity in HIV-1-infected patients receiving abacavir-containing antiretroviral therapy.
abstract: BACKGROUND
  Current or recent use of abacavir for treating human immunodeficiency virus type 1 (HIV-1) infection has been associated with increased rates of myocardial infarction (MI). Given the role of platelet aggregation in thrombus formation in MI and the reversible nature of the abacavir association, we hypothesized that patients treated with abacavir would have increased platelet reactivity.
  
  
  METHODS
  In a prospective study in adult HIV-infected patients, we determined associations between antiretrovirals (ARVs), and in particular the nucleoside reverse transcriptase inhibitor abacavir, and platelet reactivity by measuring time-dependent platelet aggregation in response to agonists: adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), collagen, and epinephrine.
  
  
  RESULTS
  Of 120 subjects, 40 were ARV-naive and 80 ARV-treated, 40 of whom were receiving abacavir. No consistent differences in platelet reactivity were observed between the ARV-naive and ARV-treated groups. In contrast, within the ARV-treated group, abacavir-treated subjects had consistently higher percentages of platelet aggregation upon exposure to ADP, collagen, and epinephrine (P = .037, P = .022, and P = .032, respectively) and had platelets that were more sensitive to aggregation upon exposure to TRAP (P = .025).
  
  
  CONCLUSIONS
  The consistent increases in platelet reactivity observed in response to a range of agonists provides a plausible underlying mechanism to explain the reversible increased rates of MI observed in abacavir-treated patients.
authors.affiliation: HIV Molecular Research Group, School of Medicine and Medical Sciences, University College Dublin, Ireland. claudette.satchell@ucd.ie
authors.forename: Claudette S
authors.initials: CS
authors.lastname: Satchell
authors.forename: Jane A
authors.initials: JA
authors.lastname: O'Halloran
authors.forename: Aoife G
authors.initials: AG
authors.lastname: Cotter
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Peace
authors.forename: Eileen F
authors.initials: EF
authors.lastname: O'Connor
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Tedesco
authors.forename: Eoin R
authors.initials: ER
authors.lastname: Feeney
authors.forename: John S
authors.initials: JS
authors.lastname: Lambert
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Sheehan
authors.forename: Dermot
authors.initials: D
authors.lastname: Kenny
authors.forename: Patrick W G
authors.initials: PW
authors.lastname: Mallon
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D015331:Cohort Studies; D003094:Collagen / Q000494:pharmacology; D003430:Cross-Sectional Studies; D015224:Dideoxynucleosides / Q000819:agonists / Q000627:therapeutic use*; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D000099227:Abacavir
chemical_list: D000244:Adenosine Diphosphate; D003094:Collagen; D015224:Dideoxynucleosides; D004837:Epinephrine; D010446:Peptide Fragments; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C086309:thrombin receptor peptide SFLLRNP