CD4/CD8 Ratio and Cancer Risk Among Adults With HIV.

Abstract

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.

• Authors: Jessica L Castilho, Aihua Bian, Cathy A Jenkins, Bryan E Shepherd, Keith Sigel, M John Gill, Mari M Kitahata, Michael J Silverberg, Angel M Mayor, Sally B Coburn, Dorothy Wiley, Chad J Achenbach, Vincent C Marconi, Ronald J Bosch, Michael A Horberg, Charles S Rabkin, Sonia Napravnik, Richard M Novak, W Christopher Mathews, Jennifer E Thorne, Jing Sun, Keri N Althoff, Richard D Moore, Timothy R Sterling, Staci L Sudenga, North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA)
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 114 Issue 6 Pg. 854-862 (06 13 2022) ISSN: 1460-2105 [Electronic] United States
• PMID: 35292820 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

Topics

• Acquired Immunodeficiency Syndrome
• Adult
• Anus Neoplasms
• CD4 Lymphocyte Count
• CD8-Positive T-Lymphocytes
• HIV Infections (complications, epidemiology)
• Humans
• Lung Neoplasms
• Lymphoma, Non-Hodgkin
• Sarcoma, Kaposi
• United States (epidemiology)