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



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.



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 (CD14CD16), 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.



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.



These prospective longitudinal data suggest that oxidized lipoproteins may contribute to persistent immune activation on ART.
aDavid Geffen School of Medicine at University of California - Los Angeles bUCLA Department of Medicine Statistics Core, Los Angeles, California cCase Western Reserve University, Cleveland, Ohio dKeck School of Medicine at the University of Southern California, Los Angeles, California eJohns Hopkins University, Baltimore, Maryland fUniversity of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Theodoros
T
Kelesidis
Nicholas
N
Jackson
Grace A
GA
McComsey
Xiaoyan
X
Wang
David
D
Elashoff
Michael P
MP
Dube
Todd T
TT
Brown
Otto O
OO
Yang
James H
JH
Stein
Judith S
JS
Currier
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000032:analysis; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D015850:Interleukin-6 / Q000097:blood; D008074:Lipoproteins / Q000032:analysis* / Q000737:chemistry; D008137:Longitudinal Studies; D008297:Male; D009000:Monocytes / Q000737:chemistry / Q000276:immunology; D010084:Oxidation-Reduction; D011446:Prospective Studies; D000072230:Sustained Virologic Response; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology
D019380:Anti-HIV Agents; D015703:Antigens, CD; D005338:Fibrin Fibrinogen Degradation Products; C508600:IL6 protein, human; D015850:Interleukin-6; D008074:Lipoproteins; C036309:fibrin fragment D; D002097:C-Reactive Protein