Lipopolysaccharide induces platelet activation in HIV patients: the role of different viral load patterns.

Abstract

This study aimed to assess whether gut-derived lipopolysaccharide (LPS) could affect platelet function in HIV-1 patients with residual viral load. In 23 HIV-1 patients on effective antiretroviral treatment, 10 treatment-naïve HIV-1 subjects and 20 healthy subjects (HS), LPS, zonulin, markers of platelet activation and oxidative stress were evaluated. In vitro, platelets from HS were exposed to plasma from HIV-1-infected treated and untreated patients. Compared with HS, LPS was higher in treated and treatment-naïve subjects with HIV-1 (7.7±2.9, 80.9±13.7 and 75.3±22.6pg/mL, P<0.001 vs. HS) as well as serum zonulin (1.3±0.5, 6.1±1.5 and 5.3±1.7ng/mL, P<0.001 vs. HS). LPS and zonulin were correlated in HIV patients (Spearman correlation coefficient (rS)=0.73, P<0.0001). Levels of soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thromboxane B2 (TxB2 ) were higher in HIV-1-treated and treatment-naïve subjects compared with HS as well as NADPH oxidase 2 (NOX2) activation and hydrogen peroxide (H2 O2 ) production. In vitro, sCD40L, sP-selectin and TxB2 production, NOX2 activation and p47phox phosphorylation were higher in platelets exposed to plasma from HIV-1 patients with different viral load compared with the exposure to plasma from HS. This effect was blunted in platelets pre-treated with TLR4 or TLR7 inhibitors. Low-grade endotoxaemia and persistent viraemia increase platelet function with a mechanism mediated by NOX2 in patients with HIV-1 infection.