{"doi":"10.1371/journal.ppat.1009825","title":"Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART","abstract":"Clinical outcomes are inferior for individuals with HIV having suboptimal CD4 T-cell recovery during antiretroviral therapy (ART). We investigated if the levels of infection and the response to homeostatic cytokines of CD4 T-cell subsets contributed to divergent CD4 T-cell recovery and HIV reservoir during ART by studying virologically-suppressed immunologic responders (IR, achieving a CD4 cell count >500 cells/μL on or before two years after ART initiation), and virologically-suppressed suboptimal responders (ISR, did not achieve a CD4 cell count >500 cells/μL in the first two years after ART initiation). Compared to IR, ISR demonstrated higher levels of HIV-DNA in naïve, central (CM), transitional (TM), and effector (EM) memory CD4 T-cells in blood, both pre- and on-ART, and specifically in CM CD4 T-cells in LN on-ART. Furthermore, ISR had higher pre-ART plasma levels of IL-7 and IL-15, cytokines regulating T-cell homeostasis. Notably, pre-ART PD-1 and TIGIT expression levels were higher in blood CM and TM CD4 T-cells for ISR; this was associated with a significantly lower fold-changes in HIV-DNA levels between pre- and on-ART time points exclusively on CM and TM T-cell subsets, but not naïve or EM T-cells. Finally, the frequency of CM CD4 T-cells expressing PD-1 or TIGIT pre-ART as well as plasma levels of IL-7 and IL-15 predicted HIV-DNA content on-ART. Our results establish the association between infection, T-cell homeostasis, and expression of PD-1 and TIGIT in long-lived CD4 T-cell subsets prior to ART with CD4 T-cell recovery and HIV persistence on-ART.","journal":"PLoS Pathogens","year":2021,"id":169472,"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":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":244982,"name":"Susan Pereira Ribeiro","orcid":"0000-0002-3127-3138","position":1,"is_corresponding":false},{"id":399936,"name":"Amélie Pagliuzza","orcid":"0000-0001-8124-2607","position":2,"is_corresponding":false},{"id":468255,"name":"Khader Ghneim","orcid":"0000-0003-0548-1942","position":3,"is_corresponding":false},{"id":700426,"name":"Anum N. 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Delman","orcid":"0000-0003-2387-0378","position":11,"is_corresponding":false},{"id":700427,"name":"Theron Stuart","orcid":"0000-0002-5870-8584","position":12,"is_corresponding":false},{"id":574693,"name":"Michael Lowe","orcid":"0000-0003-4853-7352","position":13,"is_corresponding":false},{"id":241757,"name":"Jason M. Brenchley","orcid":"0000-0001-8357-2984","position":14,"is_corresponding":false},{"id":247224,"name":"Cynthia A. Derdeyn","orcid":"0000-0002-1220-513X","position":15,"is_corresponding":false},{"id":400086,"name":"Kirk A. Easley","orcid":"0000-0003-4419-2617","position":16,"is_corresponding":false},{"id":244983,"name":"Rafick‐Pierre Sékaly","orcid":"0000-0002-7816-4828","position":17,"is_corresponding":false},{"id":235294,"name":"Nicolas Chomont","orcid":"0000-0001-9747-5018","position":18,"is_corresponding":false},{"id":244985,"name":"Mirko Paiardini","orcid":"0000-0002-7276-3600","position":19,"is_corresponding":false},{"id":104965,"name":"Vincent C. 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