Introduction and hypothesis: Human Immunodeficiency Virus (HIV)-infected subjects are at significant risk for cardiovascular disease (CVD), even after controlling for traditional risk factors. Functional studies of platelets in patients with HIV on antiretroviral therapy (ART) reveal a basally activated state, suggesting that pathological platelet activation may contribute to HIV-mediated CVD. The aim of this study was to evaluate the antiplatelet effects of aspirin and clopidogrel in ART-treated HIV subjects.
Methods: A randomized, open-label study was conducted in 55 patients. Participants were randomly assigned to clopidogrel 75 mg/d (CLO; n=20), aspirin 81 mg/d (ASA; n=20), or control (n=10). Pharmacodynamics effect was assessed at baseline and 14-day after randomization with platelet function assays, including light transmission aggregation and platelet receptor expression of PAC-1, P-selectin and CD40. Expression profiling of HUVECs co-incubated with platelets from 6 patients pre- and post- antiplatelet therapy was performed using NanoString technology.
Results: Mean age was 53.5, 43% were female, 18.5% were white and mean CD4 count was 665. Arachidonic acid-induced platelet aggregation was inhibited by ASA (-49.5±42.6 %, P<0.0001), with borderline effect by CLO (-8.7±43.2 %, P=0.03), and no difference in the control group. ADP-induced platelet aggregation was inhibited by CLO (-42.3±38.3 %, P<0.0001), with borderline effect by ASA (-16.4±23.6 %, P=0.03), and no difference in the control group. P-selectin and PAC-1 expression was significantly lower after 2 weeks of CLO (P<0.04 for each comparison) but not after ASA or control. HUVECs co-incubated with platelets from patients treated with CLO but not ASA demonstrated a reduction of IFN signaling mediators and suppression of Th1 and Th2 immune activation pathway.
Conclusions: In patients with HIV, both ASA and CLO inhibit platelet aggregation, as expected. CLO significantly reduced platelet P-selectin and PAC-1 expression which was not observed with ASA. Moreover, platelet-induced endothelial cell activation was most attenuated in CLO group. CLO treatment in HIV may represent a more robust antiplatelet and anti-inflammatory agent in patients with HIV on ART.