Associations of CD4 cell count measures with infection-related and infection-unrelated cancer risk among people with HIV

Background: People with human immunodeficiency virus (HIV) are at higher risk of infection-related cancers than the general population which could be due, in part, to immune dysfunction. Our objective was to examine associations between four CD4 count measures as indicators of immune function and infection-related and -unrelated cancer risk. Setting: We conducted a cohort study of adults with HIV who were diagnosed with cancer in Ontario, Canada. Incident cancers were identified from January 1, 1997 to December 31, 2020. Methods: We estimated adjusted hazard ratios (aHR) for the associations between CD4 measures (baseline CD4, nadir CD4, time-updated CD4, time-updated CD4:CD8) and cancer incidence rates using competing risk analyses, adjusted for socio-demographic factors, history of hepatitis B or C infection, baseline viral load, smoking, and alcohol use. Results: Among 4,771 people with HIV, contributing 59,111 person-years of observation, a total of 549 cancers were observed. Low baseline CD4 (<200 cells/µL) (aHR 2.08 [95% CI 1.38-3.13], nadir (<200 cells/µL) (aHR 2.01 [95% CI 1.49-2.71]), low time-updated CD4 (aHR 3.52 [95% CI 2.36-5.24]) and time-updated CD4:CD8 ratio (<0.4) (aHR 2.02 [95% CI 1.08-3.79]) were associated with an increased rate of infection-related cancer. No associations were observed for infection-unrelated cancers. Conclusion: Low CD4 counts and indices were associated with increased rates of infection-related cancers among people with HIV, irrespective of the CD4 measure used. Early diagnosis and linkage to care and high antiretroviral therapy uptake may lead to improved immune function and could add to cancer prevention strategies such as screening and vaccine uptake.