Cholesterol efflux responds to viral load and CD4 counts in HIV+ patients and is dampened in HIV exposed

Olivia Tort,Tuixent Escribà,Lander Egaña-Gorroño,Elisa De Lazzari,Montserrat Cofan,Emma Fernandez,José Maria Gatell,Esteban Martinez,Felipe Garcia,Mireia Arnedo

doi:10.1194/jlr.m088153

Abstract

Cholesterol efflux (CE) capacity has been inversely associated with atherosclerosis and may provide an insight on inflammation occurring in human immunodeficiency virus (HIV) individuals. We address this by studying CE in HIV patients at different stages of HIV disease progression. In this cross-sectional study, CE from ApoB-depleted plasma, lipids levels, viral load (VL), CD4+/CD8+ T-cells, high-sensitive C-reactive protein (hsCRP), and lipoprotein (a) were evaluated in untreated HIV-infected patients (UHIVs; n = 43), elite controllers (ECs; n = 8), HIV-exposed seronegative individuals (HESNs; n = 32), and healthy controls (HCs; n = 14). Among UHIVs, those with CD4+ <500 cells/mm3 presented the lowest significant CE, HDL cholesterol (HDL-C), and ApoAI levels. ECs showed similar HDL-C, ApoAI, and CE compared with HCs. Among UHIVs, CE positively correlated with CD4+ T-cell counts (Beta: 1.05; 95% CI: 1.02; 1.07), and for VL higher than 3.8 log, CE was inversely associated with VL (Beta: 0.70; 95% CI: 0.51; 0.95). Remarkably, HESNs presented higher CE (0.78 ± 0.14) than UHIVs (0.65 ± 0.17; P = 0.0005), but lower than HCs (0.90 ± 0.13; P = 0.009). hsCRP levels were highest in the UHIV group (0.45 ± 0.49). CE was sensitive to HIV disease progression. Low CE in HIV patients was associated with lower CD4+ T-cells and higher VL and hsCRP. CE was also lower in HESNs compared with HCs. Our results suggest that immune status secondary to HIV progression and exposure influence plasma HDL-CE capacity.

Highlights

untreated human immunodeficiency virus-infected patient (UHIV) patients were grouped according to their CD4+ T-cell count into UHIV CD4 500
The CD4/CD8 ratio was higher in human immunodeficiency virus-exposed seronegative individual (HESN) compared with the more immunosuppressed UHIV CD4 500 group and elite controller (EC) behaved (ANOVA one-way test; P < 0.0001) (Table 1)
We focused on the UHIV groups (CD4 500) and evaluated whether Cholesterol efflux (CE) is sensitive to CD4+ T-cell counts and human immunodeficiency virus (HIV)-1 viral load (VL)

Summary

MATERIALS AND METHODS

Samples were obtained from HIV-1-infected patients followed-up at the HIV Unit-Hospital Clinic de Barcelona. Paired t-test was used to determine statistical significance between means of HESNs and their HIV+ partners. The influence of CD4+ T-cell counts and HIV-RNA plasma VL adjusted for age on CE in UHIVs were estimated using ordinary least squares regression model. In HESNs, the effect of CD4+ T-cells (percent) and CD8+ T-cells (percent) on the CE (percent) adjusted for age was estimated using the ordinary least squares regression model. Stata: Release 13 statistical software; StataCorp LP, College Station, TX)

RESULTS

DISCUSSION

Limitations of the study and conclusions