{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:27:39Z","timestamp":1790105259505,"version":"4.0.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100010296","name":"James B. Pendleton Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010296","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI169609"],"award-info":[{"award-number":["AI169609"]}],"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":["AI106701"],"award-info":[{"award-number":["AI106701"]}],"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":["AI036214"],"award-info":[{"award-number":["AI036214"]}],"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":["AI170254"],"award-info":[{"award-number":["AI170254"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["179571"],"award-info":[{"award-number":["179571"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006447","name":"University of Zurich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yvonne Jacob Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Identifying risk factors for human immunodeficiency virus (HIV) rebound after treatment interruption is crucial for designing effective remission strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Peripheral blood mononuclear cells from participants in the Zurich HIV Primary Infection Cohort (ZPHI, n = 73) and ACTG study A5345 (n = 44) were analyzed before antiretroviral therapy (ART) interruption. We measured cell-associated HIV RNA, total HIV DNA, and proviral diversity (env gene). Immune phenotyping was conducted by flow cytometry. Cox proportional hazards (PH) models and penalized Cox PH models with an adaptive LASSO penalty identified risk factors for time to rebound (HIV RNA &amp;gt;1000\u2005copies\/mL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Late ART initiation was associated with higher rebound risk (shorter time to rebound) as compared to early ART. Higher pre-ART HIV RNA in plasma, total HIV DNA, and increased cellular HIV transcription at the time of ART interruption were associated with higher rebound risk. Higher proviral diversity was associated with higher rebound risk but only among male participants and those enrolled in the ZPHI cohort. Fewer CD4+ T cells at ART interruption, higher proportions of effector and terminally differentiated T cells, and more activated and exhausted T cells were associated with higher rebound risk, primarily in early-treated participants. No significant immunological risk factors were found in participants treated during chronic HIV. In the combined cohort, total HIV DNA and terminally differentiated CD8+ T cells appeared to be the most relevant risk factors for time to rebound, as indicated by variable selection in multivariable analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings underscore the importance of early ART initiation and suggest that tailored interventions based on virologic, immunologic, and demographic factors may help achieve sustained viral suppression.<\/jats:p>\n                    <jats:p>Clinical Trials Registration. NCT00537966 and NCT03001128.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiae585","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T23:26:40Z","timestamp":1733786800000},"page":"1221-1229","source":"Crossref","is-referenced-by-count":5,"title":["Viral and Immune Risk Factors of HIV Rebound After Interruption of Antiretroviral Therapy"],"prefix":"10.1093","volume":"231","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9927-0849","authenticated-orcid":false,"given":"Sara","family":"Gianella","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, University of California San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1628-5819","authenticated-orcid":false,"given":"Tingting","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School , Boston, Massachusetts"},{"name":"Department of Biostatistics, Harvard T. H. Chan School of Public Health, Harvard University, Boston , Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Ignacio","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, University of California San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merle","family":"Schanz","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University of Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger D","family":"Kouyos","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University of Zurich , Zurich ,","place":["Switzerland"]},{"name":"Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Caballero","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, University of California San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah C","family":"Gaitan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, University of California San Diego , La Jolla, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3637-1447","authenticated-orcid":false,"given":"Stephen","family":"Rawlings","sequence":"additional","affiliation":[{"name":"Department of Medicine, Maine Medical Center, Portland, Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Kuster","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University of Zurich , Zurich ,","place":["Switzerland"]},{"name":"Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4862-1503","authenticated-orcid":false,"given":"Karin J","family":"Metzner","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University of Zurich , Zurich ,","place":["Switzerland"]},{"name":"Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh T","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Massachusetts General Hospital, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9914-9662","authenticated-orcid":false,"given":"Jonathan Z","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-6723","authenticated-orcid":false,"given":"Huldrych F","family":"G\u00fcnthard","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University of Zurich , Zurich ,","place":["Switzerland"]},{"name":"Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davey M","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and 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