Switching from boosted PIs to dolutegravir decreases soluble CD14 and adiponectin in high cardiovascular risk people living with HIV
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 José M. , Martínez Esteban ,   the NEAT022 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 , Montforte Antonella D’Arminio , 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: April 2021

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 &lt; 0.001) and adiponectin (–11%, P &lt; 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 &lt; 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.