CD4/CD8 Ratio and Cancer Risk Among Adults With HIV

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)

doi:10.1093/jnci/djac053

CD4/CD8 Ratio and Cancer Risk Among Adults With HIV

J Natl Cancer Inst. 2022 Jun 13;114(6):854-862. doi: 10.1093/jnci/djac053.

Authors

Jessica L Castilho¹, Aihua Bian², Cathy A Jenkins², Bryan E Shepherd³, Keith Sigel⁴, M John Gill⁵, Mari M Kitahata⁶, Michael J Silverberg⁷, Angel M Mayor⁸, Sally B Coburn⁹, Dorothy Wiley¹⁰, Chad J Achenbach¹¹, Vincent C Marconi¹², Ronald J Bosch¹³, Michael A Horberg¹⁴, Charles S Rabkin¹⁵, Sonia Napravnik¹⁶, Richard M Novak¹⁷, W Christopher Mathews¹⁸, Jennifer E Thorne^{9

19}, Jing Sun²⁰, Keri N Althoff²¹, Richard D Moore²², Timothy R Sterling¹, Staci L Sudenga²³; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA)

Collaborators

North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA):
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

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
² Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
³ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
⁴ Division of Infectious Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
⁵ Department of Medicine, University of Calgary, Calgary, AB, Canada.
⁶ Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.
⁷ Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
⁸ Retrovirus Research Center, Internal Medicine Department, Universidad Central del Caribe School of Medicine, Bayamón, PR, USA.
⁹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹⁰ School of Nursing, University of California Los Angeles, Los Angeles, CA, USA.
¹¹ Division of Infectious Diseases, Department of Medicine, Northwestern Feinberg School of Medicine, Chicago, IL, USA.
¹² Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine and Rollins School of Public Health, Atlanta, GA, USA.
¹³ Department of Biostatistics, T.H. Chan Harvard School of Public Health, Boston, MA, USA.
¹⁴ Kaiser Permanente Mid-Atlantic Medical Group and Research Institute, Washington, DC, USA.
¹⁵ Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, Rockville, MD, USA.
¹⁶ Division of Infectious Diseases, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
¹⁷ Division of Infectious Diseases, Department of Medicine, University of Illinois Chicago School of Medicine, Chicago, IL, USA.
¹⁸ Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA, USA.
¹⁹ Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²⁰ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
²¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
²² Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²³ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

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

Abstract

Publication types

MeSH terms

Grants and funding