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

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• 作者：Maria Saumoy ; Jos¨¦ Luis S¨¢nchez-Quesada ; Esteban Mart¨ªnez ; Josep Maria Llibre ; Esteban Ribera ; Hern ; o Knobel ; Josep Maria Gatell ; Bonaventura Clotet ; Adrian Curran ; Jordi Curto ; Margarita Mas¨® ; Jordi Ordo?ez-Llanos ; Daniel Podzamczer
• 关键词：Raltegravir ; Ritonavir-boosted protease inhibitor ; LDL size ; LDL phenotype ; Lipoprotein-associated phospholipase A2
• 刊名：Atherosclerosis
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：225
• 期：1
• 页码：200-207
• 全文大小：528 K

文摘

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.