Association of Antiretroviral Therapy with Platelet Function and Systemic Inflammatory Response in People Living with HIV: A Cross-Sectional Study

Abstract

People living with HIV (PLWHIV) present an increased risk of adverse cardiovascular events. We aimed to assess whether antiretroviral therapy (ART) pharmacologically enhances platelet reactivity and platelet activation intensity, and explore the potential association with underlying inflammatory status. This was a cross-sectional cohort study carried out among PLWHIV on diverse ART regimens. Platelet reactivity and activation intensity were assessed using the bedside point-of-care VerifyNow assay, in P2Y12 reaction units (PRU), measurements of monocyte-platelet complexes, and P-selectin and GPIIb/IIIa expression increase, following activation with ADP, respectively. Levels of major inflammatory markers and whole blood parameters were also evaluated. In total, 71 PLWHIV, 59 on ART and 22 healthy controls, were included in this study. PRU values were significantly elevated in PLWHIV compared to controls [Mean; 257.85 vs. 196.67, p < 0.0001], but no significant differences were noted between ART-naïve or ART-experienced PLWHIV, or between TAF/TDF and ABC based regimens, similar to systemic inflammatory response. However, within-group analysis showed that PRUs were significantly higher in ABC/PI vs ABC/INSTI or TAF/TDF + PI patients, in line with levels of IL-2. PRU values did not correlate strongly with CD4 counts, viral load, or cytokine values. P-selectin and GPIIb/IIIa expression increased following ADP activation and were significantly more prominent in PLWHIV (p < 0.005). Platelet reactivity and platelet activation intensity were shown to be increased in PLWHIV, but they did not appear to be related to ART initiation, similar to the underlying systemic inflammatory response.