从增效蛋白酶抑制剂转换为多替拉韦可降低高心血管风险 HIV 感染者的可溶性 CD14 和脂联素。

Switching from boosted PIs to dolutegravir decreases soluble CD14 and adiponectin in high cardiovascular risk people living with HIV.

机构信息

Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.

Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France.

出版信息

J Antimicrob Chemother. 2021 Aug 12;76(9):2380-2393. doi: 10.1093/jac/dkab158.

DOI:10.1093/jac/dkab158

PMID:34120186

Abstract

BACKGROUND

Switching from boosted PIs to dolutegravir in people living with HIV (PLWH) with high cardiovascular risk improved plasma lipids at 48 weeks in the NEAT022 trial. Whether this strategy may have an impact on cardiovascular biomarkers is unknown.

METHODS

We assessed 48 week changes in biomarkers associated with inflammation, endothelial dysfunction, monocyte immune activation, oxidation, insulin resistance, hypercoagulability, heart failure, myocardial injury, and glomerular and tubular kidney injury.

RESULTS

Of 415 PLWH randomized in the NEAT022 study, 313 (75.4%) remained on allocated therapy and had paired samples available. Soluble CD14 (-11%, P < 0.001) and adiponectin (-11%, P < 0.001) significantly declined and high-sensitive C-reactive protein (-13%, P = 0.069) and oxidized LDL (-13%, P = 0.084) tended to decrease with dolutegravir. Switching to dolutegravir remained significantly associated with soluble CD14 and adiponectin reductions after adjustment for baseline variables. There were inverse correlations between soluble CD14 and CD4 count changes (P = 0.05), and between adiponectin and BMI changes (P < 0.001).

CONCLUSIONS

Switching from boosted PIs to dolutegravir in PLWH with high cardiovascular risk led to soluble CD14 and adiponectin reductions at 48 weeks. While decreasing soluble CD14 may entail favourable health effects in PLWH, adiponectin reduction may reflect less insulin sensitivity associated with weight gain.

摘要

背景

在心血管风险较高的 HIV 感染者（PLWH）中，从增效的蛋白酶抑制剂转换为多替拉韦可改善 NEAT022 试验中 48 周时的血浆脂质。但这种策略是否会对心血管生物标志物产生影响尚不清楚。

方法

我们评估了与炎症、内皮功能障碍、单核细胞免疫激活、氧化、胰岛素抵抗、高凝状态、心力衰竭、心肌损伤以及肾小球和肾小管肾损伤相关的生物标志物在 48 周时的变化。

结果

在 NEAT022 研究中，415 名随机分配的 PLWH 中有 313 名（75.4%）继续接受分配的治疗，并可提供配对样本。可溶性 CD14（-11%，P<0.001）和脂联素（-11%，P<0.001）显著下降，高敏 C 反应蛋白（-13%，P=0.069）和氧化型 LDL（-13%，P=0.084）则呈下降趋势。多替拉韦治疗与可溶性 CD14 和脂联素的降低仍有显著相关性，调整基线变量后仍然如此。可溶性 CD14 与 CD4 计数变化呈负相关（P=0.05），脂联素与 BMI 变化呈负相关（P<0.001）。