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

Theodoros Kelesidis, Nicholas Jackson, Grace A. McComsey, Xiaoyan Wang, David Elashoff, Michael P. Dube, Todd T Brown, O. O. Yang, J. H. Stein, J. S. Currier

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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 low- and high-density lipoproteins (HDLox, LDLox) contribute to HIV-1 related immune dysfunction. STUDY:: In the AIDS Clinical Trials Group (ACTG) A5260,234HIV-infected antiretroviral therapy (ART)-naïve participants were randomized to receive tenofovir-emtricitabine plus protease inhibitors or raltegravirand had HIV-1 RNA <50?copies/ml by week 24 and thereafter. METHODS:: Associations between biomarkers of inflammation (IL-6, hs-CRP, D-Dimer), immune activation (sCD163, sCD14, sIL-2r, CD38, HLA-DR), inflammatory monocytes (CD14+CD16+), T cell senescence (CD28, CD57) and exhaustion (PD1)and HDLox, LDLoxwere assessed at entry and afterART (week 96) with Spearman (partial) correlations. RESULTS:: HDLox declined and LDLox increasedover 96 weeks of ART. Positive associations were observed at baseline and over time between HDLox,(but not consistently for LDLox) and mostmarkers ofinflammation and immune activation (but not senescence/exhaustion),even after adjustment for multiple comparisons, demographics, entry CD4 count and HIV-1 RNA. HDLoxwaspositively associated with IL-6 (r=0.19–0.29, p?<?0.01), and sCD163 (r=0.14–0.41 p?≤?0.04) at all timepoints. CONCLUSIONS:: These prospective longitudinal data suggest that oxidized lipoproteins may contribute to persistent immune activation on ART.

Original languageEnglish (US)
JournalAIDS
DOIs
Publication statusAccepted/In press - Sep 6 2016

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Medicine(all)
  • Infectious Diseases

Cite this

Kelesidis, T., Jackson, N., McComsey, G. A., Wang, X., Elashoff, D., Dube, M. P., ... Currier, J. S. (Accepted/In press). Oxidized lipoproteins are associated with markers of inflammation andimmune activation in HIV-1 infection. AIDS. https://doi.org/10.1097/QAD.0000000000001238