TY - JOUR
T1 - CD4/CD8 Ratio and Cancer Risk among Adults with HIV
AU - Castilho, Jessica L.
AU - Bian, Aihua
AU - Jenkins, Cathy A.
AU - Shepherd, Bryan E.
AU - Sigel, Keith
AU - Gill, M. John
AU - Kitahata, Mari M.
AU - Silverberg, Michael J.
AU - Mayor, Angel M.
AU - Coburn, Sally B.
AU - Wiley, Dorothy
AU - Achenbach, Chad J.
AU - Marconi, Vincent C.
AU - Bosch, Ronald J.
AU - Horberg, Michael A.
AU - Rabkin, Charles S.
AU - Napravnik, Sonia
AU - Novak, Richard M.
AU - Mathews, W. Christopher
AU - Thorne, Jennifer E.
AU - Sun, Jing
AU - Althoff, Keri N.
AU - Moore, Richard D.
AU - Sterling, Timothy R.
AU - Sudenga, Staci L.
N1 - Publisher Copyright:
© 2022 The Author(s) 2022. Published by Oxford University Press. All rights reserved.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Background: Independent of CD4 cell count, a low CD4/CD8 ratio in 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. Methods: 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. Results: Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. 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 = 1.24 [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 <. 05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values. Conclusions: A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.
AB - Background: Independent of CD4 cell count, a low CD4/CD8 ratio in 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. Methods: 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. Results: Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. 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 = 1.24 [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 <. 05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values. Conclusions: A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.
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U2 - 10.1093/jnci/djac053
DO - 10.1093/jnci/djac053
M3 - Article
C2 - 35292820
AN - SCOPUS:85131904061
SN - 0027-8874
VL - 114
SP - 854
EP - 862
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 6
ER -