{"doi":"10.1172/jci.insight.184491","title":"IL-21 and anti-α4β7 dual therapy during ART promotes immunological and microbiome responses in SIV-infected macaques","abstract":"Despite combination antiretroviral therapy (ART), HIV causes persistent gut barrier dysfunction, immune depletion, and dysbiosis. Furthermore, ART interruption results in reservoir reactivation and rebound viremia. Both IL-21 and anti-α4β7 improve gut barrier functions, and we hypothesized that combining them would synergize as a dual therapy to improve immunological outcomes in SIV-infected rhesus macaques (RMs). We found no significant differences in CD4+ T cell reservoir size by intact proviral DNA assay. SIV rebounded in both dual-treated and control RMs following analytical therapy interruption (ATI), with time to rebound and initial rebound viremia comparable between groups; however, dual-treated RMs showed slightly better control of viral replication at the latest time points after ATI. Additionally, following ATI, dual-treated RMs showed immunological benefits, including T cell preservation and lower PD-1+ central memory T cell (TCM) frequency. Notably, PD-1+ TCMs were associated with reservoir size, which predicted viral loads (VLs) after ATI. Finally, 16S rRNA-Seq revealed better recovery from dysbiosis in treated animals, and the butyrate-producing Firmicute Roseburia predicted PD-1-expressing TCMs and VLs after ATI. PD-1+ TCMs and gut dysbiosis represent mechanisms of HIV persistence and pathogenesis, respectively. Therefore, combining IL-21 and anti-α4β7 may be an effective therapeutic strategy to improve immunological outcomes for people with HIV.","journal":"JCI Insight","year":2025,"id":520483,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":242326,"name":"María Pino","orcid":"0000-0003-4954-5215","position":1,"is_corresponding":false},{"id":296005,"name":"Arpan Acharya","orcid":"0000-0003-2721-1062","position":2,"is_corresponding":false},{"id":1390027,"name":"Julien Clain","orcid":"0000-0002-7231-0847","position":3,"is_corresponding":false},{"id":800097,"name":"Deepanwita Bose","orcid":"0000-0003-4164-6556","position":4,"is_corresponding":false},{"id":1219726,"name":"Kevin Nguyen","orcid":"0000-0002-4348-1110","position":5,"is_corresponding":false},{"id":244966,"name":"Justin Harper","orcid":"0000-0002-6948-3501","position":6,"is_corresponding":false},{"id":258352,"name":"François Villinger","orcid":"0000-0002-7790-2008","position":7,"is_corresponding":false},{"id":244985,"name":"Mirko Paiardini","orcid":"0000-0002-7276-3600","position":8,"is_corresponding":false},{"id":69434,"name":"Siddappa N. Byrareddy","orcid":"0000-0002-6889-4640","position":9,"is_corresponding":false},{"id":476979,"name":"Samuel D. Johnson","orcid":"0000-0002-9978-6968","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:28.470782Z","pmid":"39903521","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}