1. Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption.
- Author
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Pereira Ribeiro S, Strongin Z, Soudeyns H, Ten-Caten F, Ghneim K, Pacheco Sanchez G, Xavier de Medeiros G, Del Rio Estrada PM, Pelletier AN, Hoang T, Nguyen K, Harper J, Jean S, Wallace C, Balderas R, Lifson JD, Raghunathan G, Rimmer E, Pastuskova C, Wu G, Micci L, Ribeiro RM, Chan CN, Estes JD, Silvestri G, Gorman DM, Howell BJ, Hazuda DJ, Paiardini M, and Sekaly RP
- Subjects
- Animals, CD4-Positive T-Lymphocytes immunology, Treatment Interruption, Macaca mulatta, Simian Immunodeficiency Virus immunology, Simian Acquired Immunodeficiency Syndrome immunology, Simian Acquired Immunodeficiency Syndrome drug therapy, Simian Acquired Immunodeficiency Syndrome virology, Viral Load, Interleukin-10 metabolism, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor metabolism, CD8-Positive T-Lymphocytes immunology
- Abstract
Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac
239 -infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12 weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24 weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8+ T cells in lymph nodes and reduced expression of BCL-2 in CD4+ T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4+ and CD8+ T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART., (© 2024. The Author(s).)- Published
- 2024
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