1651. Oxidized HDL is Associated with Biomarkers of Inflammation and Immune Activation in Untreated and Treated HIV Infection
Session: Poster Abstract Session: HIV: Cardiovascular Disease in HIV
Saturday, October 10, 2015
Room: Poster Hall
Background: We have shown that HIV-1 infected subjects have abnormal levels of oxidized HDL (HDLox). No clinical trials have assessed the association between HDLox and immune activation after antiretroviral therapy (ART) initiation.

Methods: In ACTG A5260s, 328 HIV-infected treatment-naive subjects were randomized to tenofovir-emtricitabine plus either atazanavir-ritonavir (r), darunavir-r, or raltegravir. Plasma biomarkers of inflammation, immune activation were determined by ELISA and HDLox by an assay that measures lipid peroxidation per mg/dl of HDL. Cellular activation markers were determined by flow cytometry. A general linear model was used to test for treatment group differences for change in HDL (ox) after 96 weeks. Associations between markers of immune activation and HDLox were assessed prior to (entry) and on ART (week 96) in subjects who achieved HIV-1 RNA <50 copies/ml by week 24 (n=234) with Spearman (partial) correlations. 

Results: Compared to baseline, markers of inflammation and immune activation decreased at 96 weeks (data not shown). HDLox did not change with ART (Table 1, p>0.1 for all pairwise comparisons). Positive associations were observed at 0, 96 weeks and over time between HDLox and several inflammatory and immune activation markers even after adjustment for demographics, entry CD4 count and HIV-1 RNA (Table 2).

ATV/RTV

RAL

DRV/RTV

HDLox (ratio to control)

0.9  (0.75, 1.09)

0.95 (0.79, 1.15)

0.86 (0.74, 1.09)

HDL (mg/dl)

1.11 (0.96, 1.31)

1.12 (0.94, 1.29)

1.13 (0.93, 1.28)

Table 1: Fold change from baseline (96 weeks) (Median, Q1,Q3); ratios of 1.0 mean no change

Entry

96 weeks

Δ Wk 96-0

hsCRP

0.22 (<0.01)

0.18 (0.01)

0.21 (0.004)

IL-6

0.19 (<0.01)

0.26 (<0.001)

0.25 (<0.01)

sIL-2r

0.23 (<0.01)

0.14 (0.05)

0.16 (0.03)

sCD14

0.13 (0.06)

0.01 (0.93)

0.20 (0.01)

sCD163

0.30 (<0.01)

0.19 (0.01)

0.32 (<0.01)

% CD38+DR+ CD8+T cells

0.25 (<0.01)

0.08 (0.26)

0.19 (0.01)

Table 2: Partial Spearman Correlations  between biomarkers and HDLox (p-values) matched at each timepoint

Conclusion:

Our data suggest that HDLox levels did not change with ART and were associated with inflammation and immune activation before and after ART. Further studies are needed to understand whether HDLox mediates or reflects immune activation in HIV-1 infection.

Theodoros Kelesidis, MD, PhD1, Nicholas Jackson, PhD2, Grace a Mccomsey, MD, FIDSA3, Todd Brown, MD, PhD4, Xiaoyan Wang, PhD2, Otto Yang, MD5, James Stein, MD6 and Judith Currier, MD, MSc, FIDSA7, (1)David Geffen School of Medicine at UCLA, Los Angeles, CA, (2)David Geffen School of Medicine at UCLA, Los Angeles, CA, (3)Case Western Reserve University, Cleveland, OH, (4)Johns Hopkins University, Baltimore, MD, (5)David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, (6)University of Wisconsin School of Medicine and Public Health, MADISON, WI, (7)UCLA, Los Angeles, CA

Disclosures:

T. Kelesidis, None

N. Jackson, None

G. A. Mccomsey, BMS: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium
GSK: Consultant and Grant Investigator , Consulting fee and Research grant
Gilead: Consultant and Grant Investigator , Consulting fee and Research grant
Merck: Speaker's Bureau , Speaker honorarium

T. Brown, None

X. Wang, None

O. Yang, None

J. Stein, None

J. Currier, None

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