Early antiretroviral therapy favors post-treatment SIV control associated with the expansion of enhanced memory CD8+ T-cells

Caroline Passaes (), Delphine Desjardins, Anaïs Chapel, Valérie Monceaux, Julien Lemaitre, Adeline Mélard, Federico Perdomo-Celis, Cyril Planchais, Maël Gourvès, Nastasia Dimant, Annie David, Nathalie Dereuddre-Bosquet, Aurélie Barrail-Tran, Hélène Gouget, Céline Guillaume, Francis Relouzat, Olivier Lambotte, Jérémie Guedj, Michaela Müller-Trutwin, Hugo Mouquet, Christine Rouzioux, Véronique Avettand-Fenoël, Roger Le Grand and Asier Sáez-Cirión ()
Additional contact information
Caroline Passaes: Université Paris Cité, Viral Reservoirs and Immune Control Unit
Delphine Desjardins: Université Paris-Saclay, CEA, INSERM, UMR1184, Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT Department)
Anaïs Chapel: Université Paris Cité, Viral Reservoirs and Immune Control Unit
Valérie Monceaux: Université Paris Cité, Viral Reservoirs and Immune Control Unit
Julien Lemaitre: Université Paris-Saclay, CEA, INSERM, UMR1184, Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT Department)
Adeline Mélard: Université Paris Cité; INSERM, U1016; CNRS
Federico Perdomo-Celis: Université Paris Cité, HIV Inflammation and Persistence Unit
Cyril Planchais: Institut Pasteur, Université Paris Cité, INSERM U1222, Humoral Immunology Unit
Maël Gourvès: Université Paris Cité, Viral Reservoirs and Immune Control Unit
Nastasia Dimant: Université Paris-Saclay, CEA, INSERM, UMR1184, Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT Department)
Annie David: Université Paris Cité, HIV Inflammation and Persistence Unit
Nathalie Dereuddre-Bosquet: Université Paris-Saclay, CEA, INSERM, UMR1184, Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT Department)
Aurélie Barrail-Tran: Université Paris-Saclay, CEA, INSERM, UMR1184, Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT Department)
Hélène Gouget: Université Paris-Saclay, CEA, INSERM, UMR1184, Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT Department)
Céline Guillaume: Université Paris-Saclay, CEA, INSERM, UMR1184, Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT Department)
Francis Relouzat: Université Paris-Saclay, CEA, INSERM, UMR1184, Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT Department)
Olivier Lambotte: Université Paris-Saclay, CEA, INSERM, UMR1184, Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT Department)
Jérémie Guedj: Université Paris Cité, IAME, INSERM
Michaela Müller-Trutwin: Université Paris Cité, HIV Inflammation and Persistence Unit
Hugo Mouquet: Institut Pasteur, Université Paris Cité, INSERM U1222, Humoral Immunology Unit
Christine Rouzioux: Université Paris Cité/APHP Hôpital Necker - Enfants Malades
Véronique Avettand-Fenoël: Université Paris Cité; INSERM, U1016; CNRS
Roger Le Grand: Université Paris-Saclay, CEA, INSERM, UMR1184, Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT Department)
Asier Sáez-Cirión: Université Paris Cité, Viral Reservoirs and Immune Control Unit

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract HIV remission can be achieved in some people, called post-treatment HIV controllers, after antiretroviral treatment discontinuation. Treatment initiation close to the time of infection was suggested to favor post-treatment control, but the circumstances and mechanisms leading to this outcome remain unclear. Here we evaluate the impact of early (week 4) vs. late (week 24 post-infection) treatment initiation in SIVmac251-infected male cynomolgus macaques receiving 2 years of therapy before analytical treatment interruption. We show that early treatment strongly promotes post-treatment control, which is not related to a lower frequency of infected cells at treatment interruption. Rather, early treatment favors the development of long-term memory CD8+ T cells with enhanced proliferative and SIV suppressive capacity that are able to mediate a robust secondary-like response upon viral rebound. Our model allows us to formally demonstrate a link between treatment initiation during primary infection and the promotion of post-treatment control and provides results that may guide the development of new immunotherapies for HIV remission.

Date: 2024
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DOI: 10.1038/s41467-023-44389-3

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