{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T23:55:51Z","timestamp":1767916551078,"version":"3.49.0"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SHCS","award":["836"],"award-info":[{"award-number":["836"]}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["201369"],"award-info":[{"award-number":["201369"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"SHCS Research Foundation"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Increased blood leukocytes are associated with all-cause mortality and death from coronary disease and cancer in the general population. Limited information is available in people with HIV.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed blood leukocytes in 1850 participants of the Swiss HIV Cohort Study who died (2000\u20132023) and 1850 matched controls (median age at death 52 years, 77% male, 77% with suppressed HIV RNA on antiretroviral therapy). We assessed uni-\/multivariable odds ratios (OR) for all-cause mortality, considering major clinical and HIV-related mortality risk factors, leukocytes measured &gt;1 year before death (primary analysis) and in the latest available blood sample, and potential confounders for leukocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Leukocytes showed a U-shaped association with mortality. At a median of 433 (interquartile range [IQR], 396\u2013495) days before death, multivariable-adjusted OR for death in the highest (leukocytes \u22657730\/\u03bcL) vs. middle quintile (leukocytes 5290\u20136260\/\u03bcL) was 1.56 (95% confidence interval, 1.20\u20132.02). Multivariable-adjusted OR in the lowest (leukocytes \u22644250\/\u03bcL) vs. middle leukocyte quintile was 1.51 (1.14\u20132.01). For comparison, death-OR for hypertension, diabetes and current smoking were 1.27 (1.06\u20131.53), 1.91 (1.41\u20132.57), and 2.72 (2.14\u20133.45), respectively. Leukocytosis was uncommon (cases, 4.4% vs. controls, 2.3%; p\u2009=\u20090.004). The effect size of the highest leukocyte quintile increased in the latest blood sample (median 86 [IQR], 43\u2013152 days before death; OR=1.99 [1.44\u20132.76]). High leukocytes were associated with death from non-AIDS\/non-hepatic cancer, cardiovascular, and respiratory causes. Low leukocytes were associated with liver-related death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>High leukocytes, measured &gt;1 year before death and mostly within the normal range, are independently associated with mortality in people with HIV in Switzerland.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0340678","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T18:26:57Z","timestamp":1767896817000},"page":"e0340678","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of leukocyte count with death in people with HIV: A longitudinal study over 24 years"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2171-9850","authenticated-orcid":true,"given":"Zoe","family":"Klein","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia C.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella C.","family":"Schoepf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Weber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian W.","family":"Thorball","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lene","family":"Ryom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neeltje 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R.","family":"Kahlert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enos","family":"Bernasconi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Cavassini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8054-0044","authenticated-orcid":true,"given":"Annalisa","family":"Marinosci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Fellay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger D.","family":"Kouyos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-6723","authenticated-orcid":true,"given":"Huldrych 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leukocyte oxidative metabolism in cigarette smokers","volume":"126","author":"PW Ludwig","year":"1982","journal-title":"Am Rev Respir Dis"},{"key":"pone.0340678.ref055","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1136\/thx.56.6.432","article-title":"Enhanced neutrophil response in chronic obstructive pulmonary disease","volume":"56","author":"A Noguera","year":"2001","journal-title":"Thorax"},{"issue":"2","key":"pone.0340678.ref056","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis \u2014 An inflammatory disease","volume":"340","author":"R Ross","year":"1999","journal-title":"New England Journal of Medicine"},{"issue":"2","key":"pone.0340678.ref057","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S0272-6386(03)00650-4","article-title":"Leukocytosis, hypoalbuminemia, and the risk for chronic kidney disease in US adults","volume":"42","author":"TP Erlinger","year":"2003","journal-title":"Am 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