TY - JOUR
T1 - Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection
AU - Kelesidis, Theodoros
AU - Jackson, Nicholas
AU - McComsey, Grace A.
AU - Wang, Xiaoyan
AU - Elashoff, David
AU - Dube, Michael P.
AU - Brown, Todd T.
AU - Yang, Otto O.
AU - Stein, James H.
AU - Currier, Judith S.
N1 - Funding Information:
This research was supported by NIH grants HL095132, HL095126, AI068636, AI068634, AI69471, AI069501 and AI56933, NIH/NCATS Grant # UL1TR000124, NIH K08AI08272. The study received additional financial support from Gilead, Merck, Bristol Myers Squibb, Janssen. The project described was supported by Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701 from the National Institute of Allergy and Infectious Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or any of the funders.
Publisher Copyright:
Copyright © 2016 Wolters Kluwer Health, Inc.
PY - 2016/11/13
Y1 - 2016/11/13
N2 - 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.
AB - 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.
KW - HIV
KW - Immune activation
KW - Inflammation
KW - Oxidized lipoproteins
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U2 - 10.1097/QAD.0000000000001238
DO - 10.1097/QAD.0000000000001238
M3 - Article
C2 - 27603288
AN - SCOPUS:84986236297
SN - 0269-9370
VL - 30
SP - 2625
EP - 2633
JO - AIDS
JF - AIDS
IS - 17
ER -