Background:  Although dyslipidemia, inflammation, and endothelial dysfunction have been linked to increased cardiovascular disease (CVD) observed with HIV-1 infection and ART, the role of platelets is yet to be determined. We hypothesised that HIV infection would disrupt platelet reactivity.

Methods:  We compared platelet reactivity in 20 fasted HIV⁺ subjects and 20 matched HIV^– controls by measuring time-dependent platelet aggregation (by light absorbance) upon exposure to increasing concentrations of platelet agonists adenosine diphosphate (ADP), collagen, epinephrine, and thrombin receptor-activating peptide (TRAP). We analyzed relationships between platelet aggregation and demographic, treatment-related and inflammatory parameters using regression with data presented as median [IQR] unless otherwise stated.

Results:  Groups were matched for age (HIV⁺ mean [SD] 34 [9] years vs 34 [8] years for control) and gender (both groups 65% male). In the HIV⁺ group, mean [SD] CD4⁺ T cell count was 329 [204] cells/µL, HIV RNA was 50 [597] copies/mL with 80% on ART. In the HIV⁺ group, both ADP and TRAP induced less platelet aggregation at sub-maximal concentrations in a pattern suggesting non-competitive inhibition (ADP 70 [13]% vs 77 [15]% aggregation at 10 mM, p = 0.035; TRAP 75 [15]% vs 82 [12]% at 10 mM, p = 0.011 and 79 [11]% vs 86 [14]% at 20 µM, p = 0.012). In contrast collagen and epinephrine affected platelet aggregation in a pattern suggesting competitive inhibition. Collagen induced less aggregation at mid-range concentrations (5 [13]% vs 23 [61]%, at 0.07 mg/mL, p = 0.007 and 65 [27]% vs 73 [19]% at 0.14 mg/mL, p = 0.014) with the concentration of collagen required to induce 50% aggregation (EC₅₀) higher in the HIV⁺ group (0.11 [0.06] mg/mL vs 0.08 [0.03], p = 0.012). In contrast, the EC₅₀ for epinephrine was lower in the HIV⁺ group (4.19 [7.47] mM vs 19.7 [109.58] mM, p = 0.014). In multivariate regression, CD8 percentage and being HIV⁺ were independently associated with ADP-induced and TRAP-induced platelet aggregation respectively while higher neutrophil count and lower diastolic blood pressure were independently associated with collagen-induced platelet aggregation.

Conclusions:  This is the first study to show platelet dysfunction at multiple levels in HIV⁺ subjects with both clinical and HIV parameters associated. Further research into underlying mechanisms and examining the effect of ART is needed to determine how platelet dysfunction links to CVD in HIV⁺ patients.