Background:  Increased rates of cardiovascular disease (CVD) have been described in HIV-infected patients on antiretroviral therapy (ART) with a reversible increased risk of myocardial infarction (MI) observed in patients on abacavir (ABC) -containing ART. We hypothesized that patients on ABC would have increased platelet reactivity.

Methods:  We completed a prospective study to assess platelet function in 58 ART-treated, HIV-infected patients attending the Mater Misericordiae University Hospital, Dublin, 30 of whom were on ABC-containing ART (ABC group) and 28 who were on non-ABC-containing ART (no ABC group). Platelet reactivity was assessed on fasting blood by measuring time-dependent platelet aggregation (by light absorbance) upon exposure to increasing concentrations of platelet agonists; ADP, collagen, epinephrine and thrombin receptor activating peptide (TRAP). We used parametric analysis to determine between-group differences in platelet aggregation and linear regression to control for potential confounders with data presented as mean [SD] unless otherwise stated.

Results:  Groups were well matched for age (ABC group 38 [10] years versus 35 [10] in non-ABC group), gender (67% male versus 64% male respectively) and ethnicity (63% versus 54% respectively being Caucasian); 22 (79%) versus 20 (71%) had HIV RNA <50 copies/ml. Platelet reactivity was increased in the ABC group with ADP, collagen, and epinephrine inducing more platelet aggregation at sub-maximal agonist concentrations (ADP 30 [25]% versus 18 [18]% aggregation at 1.25 µM, p = 0.032; collagen 13 [23]% versus 1 [4]% at 35.6 µg/mL, p = 0.009:  epinephrine 31 [20]% versus 21 [17]% at 1.25 µM, p = 0.043). Although aggregation was increased with exposure to TRAP (12 [19]% versus 5 [2]% at 1.25µM), this did not reach statistical significance (P=0.06).These differences remained significant when controlled for gender, age, ethnicity, mode of HIV acquisition, smoking history, diabetes, family history of CVD, systolic blood pressure, use of other classes of ART, use of aspirin and methadone and CD3⁺, CD4⁺, and CD8⁺ T cell count.

Conclusions:  This study demonstrates consistently hyper reactive platelets in patients on ABC-containing ART and may help explain the increased rates of MI in ABC-treated patients. Further research is required to determine if this effect is reversible.