{"doi":"10.1038/s41590-024-01952-4","title":"Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption","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)mac239-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. When monkeys are infected with a virus similar to HIV, treated with antiretroviral therapy (ART), and are administered a ‘combo therapy’ made of antibodies against molecules that inhibit immune responses, they control viral rebound when ART is discontinued for more than 6 months","journal":"Nature Immunology","year":2024,"id":423902,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":248188,"name":"Zachary Strongin","orcid":null,"position":1,"is_corresponding":false},{"id":1219724,"name":"Hugo Soudeyns","orcid":"0000-0001-5857-3176","position":2,"is_corresponding":false},{"id":1049860,"name":"Felipe ten-Caten","orcid":"0000-0001-7771-1490","position":3,"is_corresponding":false},{"id":468255,"name":"Khader Ghneim","orcid":"0000-0003-0548-1942","position":4,"is_corresponding":false},{"id":644001,"name":"Gabriela Pacheco Sánchez","orcid":"0000-0002-0394-0589","position":5,"is_corresponding":false},{"id":1219725,"name":"Giuliana Xavier de Medeiros","orcid":"0000-0003-0464-3188","position":6,"is_corresponding":false},{"id":555695,"name":"Perla M. 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