Long-term effects on subclinical cardiovascular disease of switching from boosted protease inhibitors to dolutegravir.

Abstract

BACKGROUND:

In the NEAT022 trial, switching from boosted PIs (PI/r) to dolutegravir in people with HIV (PWH) with high cardiovascular risk decreased plasma lipids, soluble CD14 and adiponectin, and showed consistent favourable, although non-significant, effects on carotid intima-media thickness (CIMT) progression at 48 weeks. We hereby communicate planned final 96 week results on biomarker changes and CIMT progression.

METHODS:

PWH on a PI/r-based triple therapy regimen were randomly assigned (1:1) to switch the PI/r component to dolutegravir either immediately (DTG-I group) or after 48 weeks (DTG-D group) and were followed up to 96 weeks. We assessed 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, and right and left CIMT progression at 48 and 96 weeks.

RESULTS:

Of 415 PWH randomized, 287 (69%) and 143 (34%) contributed to the biomarker and CIMT substudies respectively. There were significant 96 week changes in biomarkers associated with inflammation, immune activation, oxidation, insulin resistance and myocardial injury. Most changes were favourable, except for adiponectin reduction, which may suggest higher insulin resistance. We were unable to detect significant changes in the progression of CIMT between arms or within arms at 96 weeks.

DISCUSSION:

After 96 weeks, switching from PI/r to dolutegravir in PWH with high cardiovascular risk led to significant changes in several biomarkers associated with cardiovascular disease. Although most changes were favourable, adiponectin reduction was not. There were non-significant changes in CIMT progression.

• Authors: Ana González-Cordón, Lambert Assoumou, Graeme Moyle, Laura Waters, Margaret Johnson, Pere Domingo, Julie Fox, Hans-Jürgen Stellbrink, Giovanni Guaraldi, Mar Masiá, Mark Gompels, Stephane De Wit, Eric Florence, Stefan Esser, François Raffi, Georg Behrens, Anton Pozniak, Jose M Gatell, Esteban Martínez, NEAT 022 Study Group
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 78 Issue 9 Pg. 2361-2365 (09 05 2023) ISSN: 1460-2091 [Electronic] England
• PMID: 37539492 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• dolutegravir
• HIV Protease Inhibitors
• Adiponectin
• Biomarkers
• Anti-HIV Agents

Topics

• Humans
• HIV Protease Inhibitors (therapeutic use)
• Cardiovascular Diseases (chemically induced, drug therapy)
• HIV Infections (complications, drug therapy)
• Adiponectin (therapeutic use)
• Carotid Intima-Media Thickness
• Insulin Resistance
• Biomarkers
• Inflammation
• Anti-HIV Agents (therapeutic use)