Long-term effects on subclinical cardiovascular disease of switching from boosted protease inhibitors to dolutegravir.
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
05 09 2023
05 09 2023
Historique:
received:
12
04
2023
accepted:
19
07
2023
medline:
6
9
2023
pubmed:
4
8
2023
entrez:
4
8
2023
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 37539492
pii: 7236964
doi: 10.1093/jac/dkad247
doi:
Substances chimiques
dolutegravir
DKO1W9H7M1
HIV Protease Inhibitors
0
Adiponectin
0
Biomarkers
0
Anti-HIV Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2361-2365Investigateurs
Linos Vandekerckhove
(L)
Els Caluwé
(E)
Stephane De Wit
(S)
Coca Necsoi
(C)
Eric Florence
(E)
Maartje Van Frankenhuijsen
(M)
François Raffi
(F)
Clotilde Allavena
(C)
Véronique Reliquet
(V)
David Boutoille
(D)
Morane Cavellec
(M)
Elisabeth André-Garnier
(E)
Audrey Rodallec
(A)
Thierry Le Tourneau
(T)
Jérôme Connault
(J)
Jean-Michel Molina
(JM)
Samuel Ferret
(S)
Miresta Previlon
(M)
Yazdan Yazdanpanah
(Y)
Roland Landman
(R)
Véronique Joly
(V)
Adriana Pinto
(A)
Christine Katlama
(C)
Fabienne Caby
(F)
Nadine Ktorza
(N)
Luminita Schneider
(L)
Christoph Stephan
(C)
Timo Wolf
(T)
Gundolf Schüttfort
(G)
Juergen Rockstroh
(J)
Jan-Christian Wasmuth
(JC)
Carolynne Schwarze-Zander
(C)
Christoph Boesecke
(C)
Hans-Jurgen Stellbrink
(HJ)
Christian Hoffmann
(C)
Michael Sabranski
(M)
Stephan Esser
(S)
Robert Jablonka
(R)
Heidi Wiehler
(H)
Georg Behrens
(G)
Matthias Stoll
(M)
Gerrit Ahrenstorf
(G)
Giovanni Guaraldi
(G)
Giulia Nardini
(G)
Barbara Beghetto
(B)
Antonella D'Arminio Montforte
(A)
Teresa Bini
(T)
Viola Cogliandro
(V)
Massimo Di Pietro
(M)
Francesco Maria Fusco
(FM)
Massimo Galli
(M)
Stefano Rusconi
(S)
Andrea Giacomelli
(A)
Paola Meraviglia
(P)
Esteban Martinez
(E)
Ana González-Cordón
(A)
José Maria Gatell
(JM)
Berta Torres
(B)
Pere Domingo
(P)
Gracia Mateo
(G)
Mar Gutierrez
(M)
Joaquin Portilla
(J)
Esperanza Merino
(E)
Sergio Reus
(S)
Vicente Boix
(V)
Mar Masia
(M)
Félix Gutiérrez
(F)
Sergio Padilla
(S)
Bonaventura Clotet
(B)
Eugenia Negredo
(E)
Anna Bonjoch
(A)
José L Casado
(JL)
Sara Bañón-Escandell
(S)
Jose Saban
(J)
Africa Duque
(A)
Daniel Podzamczer
(D)
Maria Saumoy
(M)
Laura Acerete
(L)
Juan Gonzalez-Garcia
(J)
José Ignacio Bernardino
(JI)
José Ramón Arribas
(JR)
Victor Hontañón
(V)
Graeme Moyle
(G)
Nicole Pagani
(N)
Margherita Bracchi
(M)
Jaime Vera
(J)
Amanda Clarke
(A)
Tanya Adams
(T)
Celia Richardson
(C)
Alan Winston
(A)
Borja Mora-Peris
(B)
Scott Mullaney
(S)
Laura Waters
(L)
Nahum de Esteban
(N)
Ana Milinkovic
(A)
Sarah Pett
(S)
Julie Fox
(J)
Juan Manuel Tiraboschi
(JM)
Margaret Johnson
(M)
Mike Youle
(M)
Chloe Orkin
(C)
Simon Rackstraw
(S)
James Hand
(J)
Mark Gompels
(M)
Louise Jennings
(L)
Jane Nicholls
(J)
Sarah Johnston
(S)
Informations de 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: journals.permissions@oup.com.