载脂蛋白 LDL 亚类和脂蛋白磷脂酶 A2 活性在转为服用拉替拉韦的 HIV 感染者中的变化：螺旋 substudy。

LDL subclasses and lipoprotein-phospholipase A2 activity in suppressed HIV-infected patients switching to raltegravir: Spiral substudy.

机构信息

HIV Unit, Infectious Disease Service, Bellvitge University Hospital, Bellvitge Biomedical Research Institute, C/ Feixa Llarga s/n., Hospitalet de Llobregat, 08907 Barcelona, Spain.

出版信息

Atherosclerosis. 2012 Nov;225(1):200-7. doi: 10.1016/j.atherosclerosis.2012.08.010. Epub 2012 Sep 6.

DOI:10.1016/j.atherosclerosis.2012.08.010

PMID:23017355

Abstract

OBJECTIVE

To analyze the effect of switching the ritonavir-boosted protease inhibitor (PI/r) in a stable combined antiretroviral therapy (cART) regimen to raltegravir on low-density lipoprotein (LDL) particles, and lipoprotein-associated phospholipase A2 (Lp-PLA2).

DESIGN

Substudy of a multicenter randomized trial that compared the efficacy of switching a PI/r to raltegravir-based cART in stable HIV-infected patients.

METHODS

LDL size and phenotype (by gel-gradient electrophoresis), Lp-PLA2 (by 2-thio-PAF [Cayman]), proprotein convertase subtilisin/kexin type 9 (PCSK9) (by ELISA), and standard lipid parameters were measured at baseline and week 48.

RESULTS

Eighty-one (PI/r n = 41 and raltegravir n = 40) patients were evaluated. No differences in baseline demographic and metabolic variables between arms were found except in apolipoprotein (Apo) B (p = 0.042). At week 48, total cholesterol (TC) (p < 0.001), LDL-c (p = 0.023), non-high density lipoprotein cholesterol non-high-density lipoprotein cholesterol (non-HDL-c) (p < 0.001), TC/HDL (p = 0.026), triglyceride (p < 0.001), Apo B (p < 0.001), Apo A-I (p = 0.004) and Lp (a) (p = 0.005) decreased in raltegravir arm compared to PI/r arm. At week 48, a shift from LDL phenotype B to the less atherogenic phenotype A was observed only in raltegravir arm (p < 0.001). LDL size increased (PI/r 2.1 nm, p = 0.019; raltegravir 3.8 nm, p = 0.001) and cholesterol content in small and dense LDL subfractions (LDL 4,5,6) decreased (PI/r p = 0.007, raltegravir p = 0.006) at week 48 in both arms. Total Lp-PLA2 activity (PI/r p = 0.037 and raltegravir p = 0.051) and PCSK9 plasma concentration decreased in both arms (PI/r p = 0.034 and raltegravir p < 0.001).

CONCLUSIONS

Switching a PI/r to a raltegravir-based cART in virologically suppressed HIV-infected patients was associated with an overall improvement in lipid profile, including a shift to a less atherogenic LDL phenotype.

摘要

目的

分析在稳定的联合抗逆转录病毒治疗（cART）方案中将利托那韦增强的蛋白酶抑制剂（PI/r）转换为拉替拉韦对低密度脂蛋白（LDL）颗粒和脂蛋白相关磷脂酶 A2（Lp-PLA2）的影响。

设计

比较在稳定的 HIV 感染患者中将 PI/r 转换为拉替拉韦为基础的 cART 的疗效的多中心随机试验的子研究。

方法

在基线和第 48 周时测量 LDL 大小和表型（通过凝胶梯度电泳）、Lp-PLA2（通过 2-硫代-PAF [Cayman]）、前蛋白转化酶枯草溶菌素/激肽释放酶 9（PCSK9）（通过 ELISA）和标准脂质参数。

结果

评估了 81 名患者（PI/r n=41，拉替拉韦 n=40）。除载脂蛋白（Apo）B 外（p=0.042），两组之间在基线人口统计学和代谢变量方面无差异。第 48 周时，总胆固醇（TC）（p<0.001）、LDL-c（p=0.023）、非高密度脂蛋白胆固醇（非-HDL-c）（p<0.001）、TC/HDL（p=0.026）、甘油三酯（p<0.001）、Apo B（p<0.001）、Apo A-I（p=0.004）和脂蛋白（a）（p=0.005）在拉替拉韦组中均低于 PI/r 组。第 48 周时，仅在拉替拉韦组中观察到 LDL 表型 B 向致动脉粥样硬化性较低表型 A 的转变（p<0.001）。LDL 大小增加（PI/r 2.1nm，p=0.019；raltegravir 3.8nm，p=0.001），小而密 LDL 亚组分（LDL 4、5、6）中的胆固醇含量降低（PI/r p=0.007，raltegravir p=0.006），第 48 周时两组均有发生。总 Lp-PLA2 活性（PI/r p=0.037，raltegravir p=0.051）和 PCSK9 血浆浓度在两组中均降低（PI/r p=0.034，raltegravir p<0.001）。