{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T10:04:45Z","timestamp":1776247485111,"version":"3.50.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI068634"],"award-info":[{"award-number":["UM1AI068634"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI106701"],"award-info":[{"award-number":["UM1AI106701"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI068636"],"award-info":[{"award-number":["UM1AI068636"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01MH112457"],"award-info":[{"award-number":["R01MH112457"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI147821"],"award-info":[{"award-number":["R01AI147821"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA051915"],"award-info":[{"award-number":["DA051915"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI068634"],"award-info":[{"award-number":["UM1AI068634"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Although cell surface immune checkpoint proteins (ICPs) such as PD-1 expressed on T cells are associated with T-cell exhaustion, HIV disease progression, and AIDS events, they have shown limited utility in predicting non-AIDS morbidity. Given that ICPs also exist in soluble forms and are elevated in ART-treated HIV infection, we tested the hypothesis that soluble ICPs may be predictive of non-AIDS events in adults initiating ART.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Utilizing a nested case\u2013control study from the AIDS Clinical Trials Group ALLRT cohort, we measured plasma levels of 15 soluble inhibitory and activating ICPs by Luminex. Participants (134 cases, 292 matched controls) were evaluated pre-ART, a year post-ART, and immediately preceding a non-AIDS event, which included myocardial infarction (MI)\/stroke, malignancy, serious bacterial infection, and nonaccidental death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Conditional logistic regression analysis determined that higher levels of soluble CD27 were associated with increased risk of non-AIDS events at all time points. Higher levels of CD40 at baseline and pre-event and CD80 at pre-event were associated with increased risk of non-AIDS events. Examining specific non-AIDS events, multiple ICPs were associated with malignancy at baseline and pre-event, whereas only higher CD27 levels were associated with increased risk of MI\/stroke at year 1 and pre-event.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>While select soluble ICPs were associated with non-AIDS events, CD27 emerged as a consistent marker irrespective of ART. Our data may offer guidance on new targets for early clinical monitoring in people with HIV who remain at greater risk of specific non-AIDS events.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ofid\/ofab570","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T22:42:50Z","timestamp":1642804970000},"source":"Crossref","is-referenced-by-count":7,"title":["Monitoring Circulating Immune Checkpoint Proteins as Predictors of Non-AIDS Morbid Events in People With HIV Initiating Antiretroviral Therapy"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2103-3421","authenticated-orcid":false,"given":"Thomas A","family":"Premeaux","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlee B","family":"Moser","sequence":"additional","affiliation":[{"name":"Center for Biostatistics in AIDS Research in the Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"McKhann","sequence":"additional","affiliation":[{"name":"Center for Biostatistics in AIDS Research in the Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Hoenigl","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of California San Diego, San Diego, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen T","family":"Yeung","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina P S","family":"Pang","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J","family":"Corley","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael M","family":"Lederman","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan L","family":"Landay","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Gianella","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of California San Diego, San Diego, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lishomwa C","family":"Ndhlovu","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, 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