Long-term effects on subclinical cardiovascular disease of switching from boosted protease inhibitors to dolutegravir
Authors: González-Cordón Ana , Assoumou Lambert , Moyle Graeme , Waters Laura , Johnson Margaret , Domingo Pere , Fox Julie , Stellbrink Hans-Jürgen , Guaraldi Giovanni , Masiá Mar , Gompels Mark , De Wit Stephane , Florence Eric , Esser Stefan , Raffi François , Behrens Georg , Pozniak Anton , Gatell Jose M , Martínez Esteban ,   NEAT 022 Study Group, Vandekerckhove Linos , Caluwé Els , De Wit Stephane , Necsoi Coca , Florence Eric , Van Frankenhuijsen Maartje , Raffi François , Allavena Clotilde , Reliquet Véronique , Boutoille David , Cavellec Morane , André-Garnier Elisabeth , Rodallec Audrey , Le Tourneau Thierry , Connault Jérôme , Molina Jean-Michel , Ferret Samuel , Previlon Miresta , Yazdanpanah Yazdan , Landman Roland , Joly Véronique , Pinto Adriana , Katlama Christine , Caby Fabienne , Ktorza Nadine , Schneider Luminita , Stephan Christoph , Wolf Timo , Schüttfort Gundolf , Rockstroh Juergen , Wasmuth Jan-Christian , Schwarze-Zander Carolynne , Boesecke Christoph , Stellbrink Hans-Jurgen , Hoffmann Christian , Sabranski Michael , Esser Stephan , Jablonka Robert , Wiehler Heidi , Behrens Georg , Stoll Matthias , Ahrenstorf Gerrit , Guaraldi Giovanni , Nardini Giulia , Beghetto Barbara , D’Arminio Montforte Antonella , Bini Teresa , Cogliandro Viola , Di Pietro Massimo , Fusco Francesco Maria , Galli Massimo , Rusconi Stefano , Giacomelli Andrea , Meraviglia Paola , Martinez Esteban , González-Cordón Ana , Gatell José Maria , Torres Berta , Domingo Pere , Mateo Gracia , Gutierrez Mar , Portilla Joaquin , Merino Esperanza , Reus Sergio , Boix Vicente , Masia Mar , Gutiérrez Félix , Padilla Sergio , Clotet Bonaventura , Negredo Eugenia , Bonjoch Anna , Casado José L , Bañón-Escandell Sara , Saban Jose , Duque Africa , Podzamczer Daniel , Saumoy Maria , Acerete Laura , Gonzalez-Garcia Juan , Bernardino José Ignacio , Arribas José Ramón , Hontañón Victor , Moyle Graeme , Pagani Nicole , Bracchi Margherita , Vera Jaime , Clarke Amanda , Adams Tanya , Richardson Celia , Winston Alan , Mora-Peris Borja , Mullaney Scott , Waters Laura , de Esteban Nahum , Milinkovic Ana , Pett Sarah , Fox Julie , Tiraboschi Juan Manuel , Johnson Margaret , Youle Mike , Orkin Chloe , Rackstraw Simon , Hand James , Gompels Mark , Jennings Louise , Nicholls Jane , Johnston Sarah 
Published: August 2023

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.