新诊断的HIV患者的高密度脂蛋白胆固醇流出能力及抗逆转录病毒疗法的影响
HDL Cholesterol Efflux Capacity in Newly Diagnosed HIV and Effects of Antiretroviral Therapy.
作者信息
Toribio Mabel, Park Min Hi, Zanni Markella V, Robbins Gregory K, Burdo Tricia H, Williams Kenneth C, Feldpausch Meghan N, Stone Lauren, Melbourne Kathleen, Grinspoon Steven K, Fitzgerald Michael L
机构信息
Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Lipid Metabolism Unit/Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
出版信息
J Clin Endocrinol Metab. 2017 Nov 1;102(11):4250-4259. doi: 10.1210/jc.2017-01334.
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.
背景
在普通人群中，高密度脂蛋白（HDL）胆固醇流出能力（HCEC）与心血管事件的发生呈负相关。既往研究提示，HIV患者的HCEC降低，启动抗逆转录病毒治疗（ART）可能改善HCEC。
目的
评估HIV患者启动ART及免疫激活情况下的HCEC。
设计与观察指标
分析了10例未接受过ART的HIV感染男性和12例前瞻性匹配的未感染HIV男性的基线HCEC。在HIV队列中，评估了elvitegravir/cobicistat/恩曲他滨/替诺福韦酯富马酸盐（E/C/F/TDF）治疗6个月后的HCEC。HCEC作为主要观察指标，通过J774小鼠巨噬细胞的胆固醇流出能力进行测定。我们的体外试验使用了两种胆固醇受体[载脂蛋白B（apoB）缺陷血清或纯化的HDL]，并使用肝脏X受体（LXR）激动剂调节细胞流出途径。
结果
中位年龄为34岁[四分位间距（IQR），27至51岁]，基线HDL为46mg/dL（IQR，38至61）。基线时，未感染HIV的受试者的HCEC显著高于感染HIV的受试者。使用apoB缺陷血清评估时，ART后HCEC显著增加（未使用LXR激动剂，基线：中位数，8.1%；IQR，7.0%至11.9%；ART后：中位数，12.9%；IQR，10.4%至21.1%；P = 0.006；使用LXR激动剂，基线，1.3%±1.3%；ART后，2.5%±1.0%；P = 0.02），尽管未达到未感染HIV受试者的水平（未使用LXR激动剂：中位数，14.9%；IQR，11.5%至19.1%；使用LXR激动剂：5.8%±1.3%）。使用纯化HDL评估时，ART后HCEC未显著增加。ART后HCEC的变化与CD14-CD16+（非经典）单核细胞百分比的变化呈负相关（ρ = -0.74，P = 0.04），与CD14+CD16-（经典）单核细胞百分比的变化呈正相关（ρ = 0.72，P = 0.045）。
结论
我们的数据提示，E/C/F/TDF可改善HCEC，且ART诱导的免疫激活降低与ART诱导的HCEC改善之间存在关联。
Zotero 插件