Switching from boosted PIs to dolutegravir decreases soluble CD14 and adiponectin in high cardiovascular risk people living with HIV.


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:
12 08 2021
Historique:
received: 27 01 2021
accepted: 23 04 2021
pubmed: 14 6 2021
medline: 29 10 2021
entrez: 13 6 2021
Statut: ppublish

Résumé

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. 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. Of 415 PLWH randomized in the NEAT022 study, 313 (75.4%) remained on allocated therapy and had paired samples available. Soluble CD14 (-11%, P < 0.001) and adiponectin (-11%, P < 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 < 0.001). 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.

Sections du résumé

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 < 0.001) and adiponectin (-11%, P < 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 < 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.

Identifiants

pubmed: 34120186
pii: 6297840
doi: 10.1093/jac/dkab158
doi:

Substances chimiques

Adiponectin 0
Heterocyclic Compounds, 3-Ring 0
Lipopolysaccharide Receptors 0
Oxazines 0
Piperazines 0
Pyridones 0
dolutegravir DKO1W9H7M1
Ritonavir O3J8G9O825

Types de publication

Equivalence Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2380-2393

Investigateurs

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 (AD)
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) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Ana González-Cordón (A)

Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.

Lambert Assoumou (L)

Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France.

Graeme Moyle (G)

Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.

Laura Waters (L)

Mortimer Market Centre, Central & North West London NHS Foundation Trust, London, UK.

Margaret Johnson (M)

Royal Free London NHS Foundation Trust, London, UK.

Pere Domingo (P)

Hospital de Sant Pau, Barcelona, Spain.

Julie Fox (J)

Guy's & St Thomas' NHS Foundation Trust, London, UK.

Hans-Jürgen Stellbrink (HJ)

Infektionsmedizinisches Centrum, Hamburg, Germany.

Giovanni Guaraldi (G)

University of Modena and Reggio Emilia, Modena, Italy.

Mar Masiá (M)

Hospital General Universitario de Elche, Elche, Spain.

Mark Gompels (M)

North Bristol NHS Trust, Bristol, UK.

Stephane De Wit (S)

Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium.

Eric Florence (E)

Universitair Ziekenhuis Antwerpen, Antwerp, Belgium.

Stefan Esser (S)

Universitätsklinikum, Essen, Germany.

François Raffi (F)

Centre Hospitalier Universitaire, Nantes, France.

Georg Behrens (G)

Medizinische Hochschule, Hannover, Germany.

Anton Pozniak (A)

Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.

José M Gatell (JM)

Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
ViiV Healthcare, Brentford, UK.

Esteban Martínez (E)

Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.

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Classifications MeSH