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

TitleOxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection.
Publication TypeJournal Article
Year of Publication2016
AuthorsKelesidis T, Jackson N, McComsey GA, Wang X, Elashoff D, Dubé MP, Brown TT, Yang OO, Stein JH, Currier JS
JournalAIDS
Volume30
Issue17
Pagination2625-2633
Date Published2016 Nov 13
ISSN1473-5571
KeywordsAdult, Anti-HIV Agents, Antigens, CD, Antiretroviral Therapy, Highly Active, C-Reactive Protein, Female, Fibrin Fibrinogen Degradation Products, HIV Infections, Humans, Inflammation, Interleukin-6, Lipoproteins, Longitudinal Studies, Male, Monocytes, Oxidation-Reduction, Prospective Studies, Sustained Virologic Response, T-Lymphocytes
Abstract

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 (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.

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.

DOI10.1097/QAD.0000000000001238
Alternate JournalAIDS
PubMed ID27603288
PubMed Central IDPMC5083154
Grant ListUM1 AI069501 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069471 / AI / NIAID NIH HHS / United States
K24 AI056933 / AI / NIAID NIH HHS / United States
K24 AI120834 / AI / NIAID NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
K08 AI108272 / AI / NIAID NIH HHS / United States
R01 HL095126 / HL / NHLBI NIH HHS / United States
R01 HL095132 / HL / NHLBI NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States
UM1 AI069481 / AI / NIAID NIH HHS / United States
P30 AI028697 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
U01 AI069471 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States