HIV-1 induces in vivo platelet activation by enhancing platelet NOX2 activity

Objectives: HIV-1 patients show increased platelet activation, but the mechanisms involved are not completely clarified. We speculated that HIV-1 might induce in vivo platelet activation by enhancing platelet NOX2-related oxidative stress. Methods: We measured soluble CD40 Ligand (sCD40L), a systemic marker of platelet activation, in 36 HIV-1 patients under effective combined antiretroviral therapy (cART) and in 10 naive HIV-1 subjects. As control, 20 healthy subjects (HS) were included. Platelet oxidative stress was measured by platelet NOX2-derived peptide (sNOX2-dp), p47(phox) translocation to platelet membrane and platelet prostaglandin F-2 alpha (8-iso-PGF(2 alpha)). Results: sCD40L was increased both in HIV-1 naive and cART patients compared to HS (p < 0.001). Platelet sNOX2-dp and 8-iso-PGF(2 alpha) were significantly higher in HIV-1 naive subjects compared to those on cART and to HS, and both were mutually correlated (R = 0.734, p < 0.001). A stepwise multivariable linear regression analysis showed that platelet sNOX2-dp (beta: 0.803, p < 0.001), HIV-1 infection (beta: 0.146, p = 0.014) and age (beta: 0.166, p = 0.001) were independently associated to sCD40L levels. Conclusions: HIV-1 infection is associated with increased platelet oxidative stress, which was related to the activation of NOX2. The independent association between platelet NOX2 activation and plasma levels of sCD40L suggest that in vivo platelet activation may be dependent upon platelet oxidative stress. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.