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: Claudette S Satchell, Jane A O'Halloran, Aoife G Cotter, Aaron J Peace, Eileen F O'Connor, Anthony F Tedesco, Eoin R Feeney, John S Lambert, Gerard J Sheehan, Dermot Kenny, Patrick W G Mallon
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 204 Issue 8 Pg. 1202-10 (Oct 15 2011) ISSN: 1537-6613 [Electronic] United States
• PMID: 21917893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dideoxynucleosides
• Peptide Fragments
• Reverse Transcriptase Inhibitors
• thrombin receptor peptide SFLLRNP
• Adenosine Diphosphate
• Collagen
• abacavir
• Epinephrine

Topics

• Adenosine Diphosphate (pharmacology)
• Adult
• Cohort Studies
• Collagen (pharmacology)
• Cross-Sectional Studies
• Dideoxynucleosides (agonists, therapeutic use)
• Drug Interactions
• Epinephrine (pharmacology)
• Female
• HIV Infections (blood, drug therapy, immunology, virology)
• HIV-1
• Humans
• Male
• Peptide Fragments (pharmacology)
• Platelet Aggregation (drug effects)
• Prospective Studies
• Reverse Transcriptase Inhibitors (pharmacology, therapeutic use)
• Statistics, Nonparametric