Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection

Objective: The pathogenesis of immune dysfunction in chronic HIV-1 infection is unclear, and a potential role for oxidized lipids has been suggested. We hypothesize that both oxidized HDL and LDL (HDLox and LDLox) contribute to HIV-1-related immune dysfunction. Study: In the AIDS Clinical Trials Group A5260, 234 HIV-infected antiretroviral therapy (ART)-naive participants were randomized to receive tenofovir-emtricitabine and protease inhibitors or raltegravir and had HIV-1 RNA less than 50 copies/ml by week 24 and thereafter. Methods: Associations between biomarkers of inflammation (IL-6, high-sensitivity C-reactive protein and D-dimer), immune activation (sCD163, sCD14, soluble IL-2 receptor, CD38 and HLA-DR), inflammatory monocytes (CD14+CD16+), T-cell senescence (CD28 and CD57) and exhaustion (PD1), and HDLox, LDLox were assessed at entry and after ART (week 96) with Spearman (partial) correlations. Results: HDLox declined and LDLox increased over 96 weeks of ART. Positive associations were observed at baseline and over time between HDLox (but not consistently for LDLox) and most markers of inflammation and immune activation (but not senescence/ exhaustion), even after adjustment for multiple comparisons, demographics, entry CD4+ cell count and HIV-1 RNA. HDLox was positively associated with IL-6 (r=0.19-0.29, P<0.01) and sCD163 (r=0.14-0.41, P≤0.04) at all time points. Conclusion: These prospective longitudinal data suggest that oxidized lipoproteins may contribute to persistent immune activation on ART.