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- Title
Atherogenicity of low-density lipoproteins after switching from a protease inhibitor to dolutegravir: a substudy of the NEAT022 study.
- Authors
Saumoy, Maria; Sánchez-Quesada, Jose Luís; Assoumou, Lambert; Gatell, José Maria; González-Cordón, Ana; Guaraldi, Giovanni; Domingo, Pere; Giacomelli, Andrea; Connault, Jérôme; Katlama, Christine; Masiá, Mar; Ordónez-Llanos, Jordi; Pozniak, Anton; Martínez, Esteban; Podzamczer, Daniel
- Abstract
<bold>Background: </bold>The aim of this study was to investigate whether switching from a ritonavir-boosted PI-based regimen to a dolutegravir-based regimen improved the atherogenic properties of LDL particles in patients with HIV.<bold>Methods: </bold>This was a substudy of the NEAT022 study (ClinicalTrials.gov NCT02098837). Adults with HIV with a Framingham score >10% or aged >50 years and being treated with a stable boosted PI-based regimen were randomized to either switch to dolutegravir or continue with boosted PI. At baseline and Week 48, we assessed atherogenic LDL properties: LDL particle size and phenotype (A, intermediate, B), oxidized LDL (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity.<bold>Results: </bold>Eighty-six participants (dolutegravir 44; PI 42) were included. Participants had a median (IQR) age of 54 (51-57) years and 79.1% were male. In the dolutegravir arm, after 48 weeks, we observed: (1) an increase in LDL size [median 1.65 Å (IQR -0.60 to 4.20); P = 0.007], correlated with the decrease in triglyceride concentration [Spearman correlation = -0.352 (P = 0.001)], with a corresponding decrease of subjects with atherogenic LDL phenotype B (36.4% to 20.5%; P = 0.039); (2) a decrease in Lp-PLA2 activity [median 1.39 μmol/min/mL (IQR -2.3 to 0.54); P = 0.002]; and (3) a decrease in ox-LDL [median 14 U/L (IQR -102 to 13); P = 0.006]. In the PI arm, none of these favourable lipid modifications was observed.<bold>Conclusions: </bold>Forty-eight weeks after switching from a PI-based to a dolutegravir-based regimen, patients with Framingham score >10% or aged >50 years showed improvement of several atherogenic lipid features, including LDL particle phenotype, ox-LDL and Lp-PLA2.
- Subjects
THERAPEUTIC use of protease inhibitors; HIV infections; ANTI-HIV agents; PYRIDINE; RESEARCH; HETEROCYCLIC compounds; RESEARCH methodology; LOW density lipoproteins; EVALUATION research; ATHEROSCLEROSIS; COMPARATIVE studies; RANDOMIZED controlled trials; RESEARCH funding; ESTERASES
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2022, Vol 77, Issue 7, p1980
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkac117