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Clinical Trial
. 2017 Nov 1;102(11):4250-4259.
doi: 10.1210/jc.2017-01334.

HDL Cholesterol Efflux Capacity in Newly Diagnosed HIV and Effects of Antiretroviral Therapy

Mabel Toribio  1 , Min Hi Park  2 , Markella V Zanni  1 , Gregory K Robbins  3 , Tricia H Burdo  4 , Kenneth C Williams  4 , Meghan N Feldpausch  1 , Lauren Stone  1 , Kathleen Melbourne  5 , Steven K Grinspoon  1 , Michael L Fitzgerald  2
Affiliations
Clinical Trial

HDL Cholesterol Efflux Capacity in Newly Diagnosed HIV and Effects of Antiretroviral Therapy

Mabel Toribio et al. J Clin Endocrinol Metab. .

Abstract

Context: In the general population, high-density lipoprotein (HDL) cholesterol efflux capacity (HCEC) relates inversely to incident cardiovascular events. Previous studies have suggested that HCEC is decreased in HIV and that antiretroviral therapy (ART) initiation might improve HCEC.

Objective: To evaluate HCEC in the context of ART initiation and immune activation in HIV.

Design and outcome measures: Baseline HCEC from 10 ART-naive HIV-infected males and 12 prospectively matched non-HIV-infected males were analyzed. In the HIV cohort, HCEC 6 months after elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) therapy was evaluated. HCEC served as the primary outcome and was measured by the ability of J774 mouse macrophages to efflux cholesterol. Our ex vivo assay used two cholesterol acceptors [apolipoprotein B (apoB)-depleted sera or purified HDL] and modulation of cellular efflux pathways using a liver X receptor (LXR) agonist.

Results: The median age was 34 years [interquartile range (IQR), 27 to 51], and baseline HDL was 46 mg/dL (IQR, 38 to 61). HCEC was significantly greater in the non-HIV-infected subjects than in the HIV-infected subjects at baseline. HCEC, assessed using apoB-depleted sera, significantly increased after ART (no LXR agonist, baseline: median, 8.1%; IQR, 7.0% to 11.9%; after ART: median, 12.9%; IQR, 10.4% to 21.1%; P = 0.006; LXR agonist, baseline, 1.3% ± 1.3%; after ART, 2.5% ± 1.0%; P = 0.02), although not to the levels in the non-HIV-infected subjects (no LXR agonist: median, 14.9%; IQR, 11.5% to 19.1%; LXR agonist: 5.8% ± 1.3%). HCEC, assessed using purified HDL, did not significantly increase after ART. The change in HCEC with ART related inversely to the change in the percentage of CD14-CD16+ (nonclassical) monocytes (ρ = -0.74, P = 0.04) and directly to the change in the percentage of CD14+CD16- (classical) monocytes (ρ = 0.72, P = 0.045).

Conclusions: Our data suggest improvement of HCEC with E/C/F/TDF and a relationship between the ART-induced decrease in immune activation and ART-induced improvement in HCEC.

Trial registration: ClinicalTrials.gov NCT01766726.

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Figures

Figure 1.
Figure 1.
HCEC with apoB-depleted sera using (a) 18 hours of LXR agonism and (b) 24 hours of LXR agonism. (a) HCEC was assessed with apoB-depleted sera and 18 hours of LXR agonism. HCEC was significantly greater in the non–HIV-infected subjects compared with the HIV-infected subjects at baseline (5.8% ± 1.3% vs 1.3% ± 1.3%, P < 0.0001). After 6 months of E/C/F/TDF, HCEC significantly increased in the HIV-infected subjects from 1.3% ± 1.3% to 2.5% ± 1.0% (P = 0.02), although not to the levels seen in the non–HIV-infected subjects. (b) HCEC was assessed with apoB-depleted sera and 24 hours of LXR agonism. At baseline, HCEC again was greater in the non–HIV-infected subjects compared with the HIV-infected subjects (15.3% ± 3.8% vs 11.6% ± 4.0%, P = 0.04). After 6 months of cART, HCEC did not significantly increase in the HIV-infected subjects under maximal stimulation of efflux using an LXR agonist (11.6% ± 4.0% to 12.7% ± 2.3%, P = 0.30).
Figure 2.
Figure 2.
HCEC with purified HDL using (a) 18 hours of LXR agonist and (b) 24 hours of LXR agonism. (a) HCEC was assessed with purified HDL and 18 hours of LXR agonism. A borderline statistically significant difference was seen in HCEC between the non–HIV-infected subjects and the HIV-infected subjects (15.1%, IQR, 13.7% to 18.0%; vs 11.2%, IQR, 5.5% to 15.2%; P = 0.046). HCEC did not increase substantially with 6 months of E/C/F/TDF under this condition (11.2%, IQR, 5.5% to 15.2% to 11.6%, IQR, 4.2% to 15.2%; P = 1.00). (b) HCEC was assessed with purified HDL and 24 hours of LXR agonism. No statistically significant difference was seen in HCEC between non–HIV-infected subjects and HIV-infected subjects at baseline (10.8% ± 4.6% vs 11.3% ± 5.1%; P = 0.82). After 6 months of cART, also no statistically significant increase in HCEC was seen using purified HDL and maximal stimulation with an LXR agonist (11.3% ± 5.1% to 12.5% ± 3.4%, P = 0.52).
Figure 3.
Figure 3.
HCEC with apoB-depleted sera and no LXR agonism was significantly greater in the non–HIV-infected subjects compared with the HIV-infected subjects at baseline (14.9%, IQR, 11.5% to 19.1% vs 8.1%, IQR, 7.0% to 11.9%; P = 0.009). Additionally, 6 months of cART led to a statistically significant increase in HCEC in HIV-infected subjects from 8.1% (IQR, 7.0% to 11.9%) to 12.9% (IQR, 10.4% to 21.1%; P = 0.006).
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