Switching from boosted PIs to dolutegravir in HIV-infected patients with high cardiovascular risk: 48 week effects on subclinical cardiovascular disease.


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:
01 11 2020
Historique:
received: 29 04 2020
accepted: 02 06 2020
pubmed: 2 8 2020
medline: 25 6 2021
entrez: 2 8 2020
Statut: ppublish

Résumé

Switching from boosted PIs to dolutegravir in virologically suppressed HIV-infected patients with high cardiovascular risk significantly decreased total cholesterol and other proatherogenic lipid fractions at 48 weeks. The impact of this strategy on subclinical cardiovascular disease is unknown. NEAT022 is a European, multicentre, open-label, randomized, non-inferiority trial. HIV-infected adults aged >50 years or with a Framingham score >10% were eligible if plasma HIV RNA was <50 copies/mL for >24 weeks on a boosted PI-based regimen. Patients were randomized 1:1 to switch from boosted PIs to dolutegravir or to continue on boosted PIs. Common carotid arteries intima-media thickness (CIMT) and pulse wave velocity (PWV) were measured following a standardized protocol in a subgroup of NEAT022 study participants at baseline and at Week 48. One hundred and fifty-six patients participated in the ultrasonography and arterial stiffness substudies, respectively. In each substudy, population characteristics did not differ between arms and matched those of the main study. At 48 weeks, patients who switched to dolutegravir had lower mean progression of both right (+4 versus +14.6 μm) and left (-6.1 versus +1.6 μm) CIMT and also a smaller increase in mean PWV (+0.18 versus +0.39 m/s) than patients continuing on boosted PIs, although differences were not statistically significant. CIMT trends were consistent across Framingham score, age and country. Inconsistent effects were seen in arterial stiffness. Relative to continuing on boosted PIs, switching to dolutegravir in virologically suppressed patients with high cardiovascular risk showed consistent favourable although non-significant trends on CIMT progression at 48 weeks.

Sections du résumé

BACKGROUND
Switching from boosted PIs to dolutegravir in virologically suppressed HIV-infected patients with high cardiovascular risk significantly decreased total cholesterol and other proatherogenic lipid fractions at 48 weeks. The impact of this strategy on subclinical cardiovascular disease is unknown.
METHODS
NEAT022 is a European, multicentre, open-label, randomized, non-inferiority trial. HIV-infected adults aged >50 years or with a Framingham score >10% were eligible if plasma HIV RNA was <50 copies/mL for >24 weeks on a boosted PI-based regimen. Patients were randomized 1:1 to switch from boosted PIs to dolutegravir or to continue on boosted PIs. Common carotid arteries intima-media thickness (CIMT) and pulse wave velocity (PWV) were measured following a standardized protocol in a subgroup of NEAT022 study participants at baseline and at Week 48.
RESULTS
One hundred and fifty-six patients participated in the ultrasonography and arterial stiffness substudies, respectively. In each substudy, population characteristics did not differ between arms and matched those of the main study. At 48 weeks, patients who switched to dolutegravir had lower mean progression of both right (+4 versus +14.6 μm) and left (-6.1 versus +1.6 μm) CIMT and also a smaller increase in mean PWV (+0.18 versus +0.39 m/s) than patients continuing on boosted PIs, although differences were not statistically significant. CIMT trends were consistent across Framingham score, age and country. Inconsistent effects were seen in arterial stiffness.
CONCLUSIONS
Relative to continuing on boosted PIs, switching to dolutegravir in virologically suppressed patients with high cardiovascular risk showed consistent favourable although non-significant trends on CIMT progression at 48 weeks.

Identifiants

pubmed: 32737482
pii: 5879495
doi: 10.1093/jac/dkaa292
doi:

Substances chimiques

Anti-HIV Agents 0
Heterocyclic Compounds, 3-Ring 0
Oxazines 0
Piperazines 0
Pyridones 0
dolutegravir DKO1W9H7M1

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3334-3343

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 Martinez (AP)
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 Portillo (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 (J)
José Ramón Arribas (J)
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) 2020. 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 Gonzalez-Cordon (A)

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

Lambert Assoumou (L)

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F75013 Paris, France.

Miguel Camafort (M)

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

Monica Domenech (M)

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

Giovanni Guaraldi (G)

University of Modena and Reggio Emilia, Modena, Italy.

Pere Domingo (P)

Hospital de Sant Pau, Barcelona, Spain.

Stefano Rusconi (S)

DIBIC Luigi Sacco, University of Milan, Milan, Italy.

François Raffi (F)

Hotel-Dieu University Hospital, Nantes, France.

Christine Katlama (C)

Hôpital Pitié-Salpêtrière, Paris, France.

Mar Masia (M)

Hospital General Universitario de Elche, Elche, Spain.

Jose I Bernardino (JI)

Hospital Universitario La Paz, Madrid, Spain.

Maria Saumoy (M)

Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.

Anton Pozniak (A)

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

Jose M Gatell (JM)

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

Esteban Martinez (E)

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

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Classifications MeSH