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of CD4 cell count, a low CD4\/CD8 ratio\u00a0in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4\/CD8 ratios predicted cancer among PWH in the United States and Canada.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined all cancer-free PWH with 1 or more CD4\/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4\/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 83\u2009893 PWH, there were 5628 incident cancers, including lung cancer (n\u2009=\u2009755), Kaposi sarcoma (n\u2009=\u2009501), non-Hodgkin lymphoma (n\u2009=\u2009497), and anal cancer (n\u2009=\u2009439). The median age at cohort entry was 43\u2009years. The overall median 6-month lagged CD4\/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4\/CD8 of 0.80, a CD4\/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio\u2009=\u20091.24 [95% confidence interval = 1.14 to 1.35]). The CD4\/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P\u2009&amp;lt;\u2009.05). Results were similar using 12-, 18-, and 24-month lagged CD4\/CD8 values.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A low CD4\/CD8 ratio up to 24\u2009months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.\u00a0<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djac053","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T23:11:44Z","timestamp":1646867504000},"page":"854-862","source":"Crossref","is-referenced-by-count":78,"title":["CD4\/CD8 Ratio and Cancer Risk Among Adults With HIV"],"prefix":"10.1093","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7599-8173","authenticated-orcid":false,"given":"Jessica L","family":"Castilho","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center , Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy A","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center , Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan E","family":"Shepherd","sequence":"additional","affiliation":[{"name":"Department\u2002 of Biostatistics, Vanderbilt University Medical Center , Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4051-4861","authenticated-orcid":false,"given":"Keith","family":"Sigel","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Mount Sinai School of Medicine , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M John","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary , Calgary, AB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5410-7175","authenticated-orcid":false,"given":"Mari M","family":"Kitahata","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington , Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9322-1395","authenticated-orcid":false,"given":"Michael J","family":"Silverberg","sequence":"additional","affiliation":[{"name":"Division of Research, Kaiser Permanente Northern California , Oakland, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7705-837X","authenticated-orcid":false,"given":"Angel M","family":"Mayor","sequence":"additional","affiliation":[{"name":"Retrovirus Research Center, Internal Medicine Department, Universidad Central del Caribe School of Medicine , Bayam\u00f3n, PR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6423-1137","authenticated-orcid":false,"given":"Sally B","family":"Coburn","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9416-473X","authenticated-orcid":false,"given":"Dorothy","family":"Wiley","sequence":"additional","affiliation":[{"name":"School of Nursing, University of California Los Angeles , Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad J","family":"Achenbach","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Northwestern Feinberg School of Medicine , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8409-4689","authenticated-orcid":false,"given":"Vincent C","family":"Marconi","sequence":"additional","affiliation":[{"name":"Division\u00a0of Infectious Diseases, Department of Medicine, Emory University School of Medicine and Rollins School of Public Health , Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J","family":"Bosch","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, T.H. 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