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Lower CD4/CD8 Ratio Boosts Cancer Risk in US/Canada HIV Group
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CROI 2020, March 8-11, 2020, Boston
Mark Mascolini
A large analysis of North Americans with HIV infection linked low CD4/CD8 ratio to a higher risk of newly diagnosed cancer [1]. The finding applied to both AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs), but not to all cancers in either group and not to all virus-related cancers.
Because research ties low CD4/CD8 ratios to NADCs and mortality, NA-ACCORD investigators asked whether a low CD4/CD8 ratio predicts cancer risk in people with HIV. Their analysis included NA-ACCORD members with CD4/CD8 data and validated cancer outcomes and excluded people with cancer diagnosed before or within 6 months of entering NA-ACCORD.
To assess potential associations between CD4/CD8 ratio and incident (newly diagnosed) cancers, the research team used a multivariable Cox model adjusted for lagged, time-varying covariates (CD4/CD8 ratio, CD4 count, HIV viral load, ever having an opportunistic infection, body mass index) and time-fixed covariates (age, sex, race/ethnicity, ever having HCV infection, ever smoked, HIV transmission risk factor).
The analysis included 75,161 cohort members, 90% of them men, with a median age of 43 at cohort entry. Racial/ethnic proportions were 44% white, 37% black, 10% Latinx, and 8% other. Median follow-up stood at 8 years and median CD4/CD8 ratio was 0.49 (interquartile range 0.27 to 0.79). During follow-up, researchers counted 5049 cancer diagnoses and 13,885 deaths.
Multivariate analysis linked lower CD4/CD8 to several cancers at the following adjusted hazard ratios (aHR) and 95% confidence intervals (CI):
-- Any cancer (50th vs 75th CD4/CD8 percentile): aHR 1.10, 95% CI 1.06 to 1.15
-- Any cancer (25th vs 75th CD4/CD8 percentile): aHR 1.28, 95% CI 1.16 to 1.41
AIDS-defining cancers
-- Non-Hodgkin lymphoma (50th vs 75th CD4/CD8 percentile): aHR 1.51, 95% CI 1.29 to 1.77
-- Non-Hodgkin lymphoma (25th vs 75th CD4/CD8 percentile): 2.58, 95% CI 1.82 to 3.67
-- Kaposi sarcoma (50th vs 75th CD4/CD8 percentile): aHR 1.33, 95% CI 1.07 to 1.64
-- Kaposi sarcoma (25th vs 75th CD4/CD8 percentile): aHR 1.66, 95% CI 1.09 to 2.53
HIV-associated cancers
-- Lung cancer (50th vs 75th CD4/CD8 percentile): aHR 1.27, 95% CI 1.14 to 1.40
-- Lung cancer (25th vs 75th CD4/CD8 percentile): aHR 1.64, 95% CI 1.28 to 2.09
-- Anal cancer (50th vs 75th CD4/CD8 percentile): aHR 1.55, 95% CI 1.33 to 1.81
-- Anal cancer (25th bs 75th CD4/CD8 percentile): aHR 2.53, 95% CI 1.80 to 3.55
Other cancers
-- Colorectal cancer (50th vs 75th CD4/CD8 percentile): aHR 1.25, 95% CI 1.02 to 1.53
-- Colorectal cancer (25th vs 75th CD4/CD8 percentile): aHR 1.57, 95% CI 0.98 to 2.53
Cancers not associated with low CD4/CD8 ratio in this analysis were cervical cancer (an AIDS-defining cancer), liver cancer, Hodgkin lymphoma, head and neck cancer, prostate cancer, and breast cancer.
The researchers noted that low CD4/CD8 ratio predicted higher cancer risk for some virus-associated cancers (non-Hodgkin lymphoma, Kaposi sarcoma, anal cancer, colorectal cancer) but not for others (cervical cancer, Hodgkin lymphoma). They suggested that further research could assess CD4/CD8 ratio as a tool to inform cancer prevention and screening in people with HIV.
Reference
1. Castilho JL, Bian Aihua, Jenkins C, et al. Increased cancer risk with lower CD4/CD8 ratio among adults with HIV in NA-ACCORD. Conference on Retroviruses and Opportunistic Infections (CROI). March 8-11, 2020. Boston. Abstract 71.
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