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

• Published in: Nature communications Vol. 15; no. 1; p. 178
• Main Authors: Passaes, Caroline, Desjardins, Delphine, Chapel, Anaïs, Monceaux, Valérie, Lemaitre, Julien, Mélard, Adeline, Perdomo-Celis, Federico, Planchais, Cyril, Gourvès, Maël, Dimant, Nastasia, David, Annie, Dereuddre-Bosquet, Nathalie, Barrail-Tran, Aurélie, Gouget, Hélène, Guillaume, Céline, Relouzat, Francis, Lambotte, Olivier, Guedj, Jérémie, Müller-Trutwin, Michaela, Mouquet, Hugo, Rouzioux, Christine, Avettand-Fenoël, Véronique, Le Grand, Roger, Sáez-Cirión, Asier
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/21; 13/31; 631/250/2152/1566; 631/250/255/1901; 631/326/596/1787; 631/326/596/2555; Animals; Anti-Retroviral Agents - therapeutic use; Antiretroviral agents; Antiretroviral therapy; Antiviral agents; CD8 antigen; CD8-Positive T-Lymphocytes; Drug therapy; HIV; HIV Infections - drug therapy; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Immunological memory; Immunotherapy; Infections; Life Sciences; Long term memory; Lymphocytes; Lymphocytes T; Male; Memory cells; multidisciplinary; Remission; Science; Science (multidisciplinary); Simian Acquired Immunodeficiency Syndrome - drug therapy; Simian Immunodeficiency Virus; Therapy; Viral Load
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-44389-3

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 SIVmac 251 -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. HIV remission has been seen in people living with HIV after the cessation of antiretroviral therapy and is termed post treatment control. Here Passaes and colleagues present an SIV model that shows early initiation of antiretroviral therapy after SIV infection is linked to improved post treatment control upon cessation of antiviral therapy and associates with the expansion of an enhanced memory pool of CD8 + T cells‘.