Background Despite suppressive antiretroviral therapy (ART), increased levels of immune activation persist in HIV-infected subjects. Statins have anti-inflammatory effects and may reduce immune activation in HIV disease. Methods SATURN-HIV is a randomized, double-blind, placebo-controlled trial assessing the effect of rosuvastatin (10mg/daily) on markers of cardiovascular risk and immune activation in ART-treated patients. T cell activation was measured by expression of CD38, HLA-DR, and PD1. Monocyte activation was measured with soluble markers (sCD14 and sCD163) and by enumeration of monocyte subpopulations and tissue factor (TF) expression. Markers of systemic and vascular inflammation and coagulation were also measured. SATURN-HIV is registered on clinicaltrials.gov, Identifier: NCT01218802 Results Rosuvastatin, compared to placebo, reduced sCD14 (−10.4% vs 0.5%p=0.006), Lp-PLA2 (−12.2% vs −1.7% p=0.0007), and IP-10 (−27.5 vs −8.2%, p=0.03) levels after 48 weeks. The proportion of TF+ patrolling (CD14DimCD16+) monocytes was also reduced by rosuvastatin (−41.6%) compared to the placebo (−18.8%, p=0.005). There was also a greater decrease in the proportions of activated (CD38+HLA-DR+) T cells between the arms (−38.1% vs −17.8%, p=0.009 for CD4+ cells and −44.8% vs −27.4%, p=0.003 for CD8+ cells). Conclusions 48 weeks of rosuvastatin treatment reduced significantly several markers of inflammation and lymphocyte and monocyte activation in ART-treated subjects.

Background Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk, and this risk correlates with markers of monocyte activation. We have shown that HIV is associated with a prothrombotic monocyte phenotype, which can be partially mitigated by statin therapy. We therefore explored the relationship between oxidized LDL particles and monocyte activation. Methods We performed phenotypic analysis of monocytes using flow cytometry on fresh whole blood in 54 patients with HIV and 24 controls without HIV. Plasma levels of oxLDL, soluble CD14, IL-6, soluble CD163 were measured by ELISA. In vitro experiments were performed using flow cytometry. Results Plasma levels of oxLDL were significantly increased in HIV-infection compared to controls (60.1 units vs 32.1 units, p<0.001). Monocyte expression of the oxLDL receptors, CD36 and Toll-like receptor 4, were also increased in HIV. OxLDL levels correlated with markers of monocyte activation, including soluble CD14, TF expression on inflammatory monocytes, and CD36. In vitro, stimulation with oxLDL, but not to LDL, resulted in expansion of inflammatory monocytes and increased monocyte expression of TF, recapitulating the monocyte profile we find in HIV disease. Conclusions OxLDL may contribute to monocyte activation and further study in the context of HIV disease is warranted.