Increased Platelet Reactivity in HIV-1-Infected Patients Receiving Abacavir-Containing Antiretroviral Therapy

• Published in: The Journal of infectious diseases Vol. 204; no. 8; pp. 1202 - 1210
• Main Authors: Satchell, Claudette S., O'Halloran, Jane A., Cotter, Aoife G., Peace, Aaron J., O'Connor, Eileen F., Tedesco, Anthony F., Feeney, Eoin R., Lambert, John S., Sheehan, Gerard J., Kenny, Dermot, Mallon, Patrick W. G.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.10.2011
• Subjects: Adenosine Diphosphate - pharmacology; Adult; Agonists; AIDS; Antiretrovirals; Biological and medical sciences; Cardiovascular diseases; Cohort Studies; Collagen - pharmacology; Collagens; Cross-Sectional Studies; Dideoxynucleosides - agonists; Dideoxynucleosides - therapeutic use; Drug Interactions; Epinephrine - pharmacology; Female; Fundamental and applied biological sciences. Psychology; HIV; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV-1; HIV/AIDS; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Microbiology; Myocardial infarction; Peptide Fragments - pharmacology; Platelet aggregation; Platelet Aggregation - drug effects; Platelets; Prospective Studies; Reactivity; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; Statistics, Nonparametric; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Immunopathology; Purine nucleoside; Antiretroviral agent; RNA-directed DNA polymerase; Enzyme; Transferases; Enzyme inhibitor; AIDS; Immune deficiency; Infection; Nucleotidyltransferases; Platelet; Treatment; Reverse transcriptase inhibitor; Viral disease; Abacavir; Nucleoside analog; Antiviral
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jir509

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 antiretro virais (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.