HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies

Objective: To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDSdefining malignancies (nADM) in the D:A:D Study and to investigate the relationship between these deaths and immunodeficiency. Design: Observational cohort study. Methods: Patients (23 437)were followed prospectively for 104 921 person-years.We used Poisson regression models to identify factors independently associated with deaths from ADM and nADM. Analyses of factors associated with mortality due to nADMwere repeated after excludingnADMknown to be associated with a specific risk factor. Results: Three hundred five patients died due to a malignancy, 298 prior to the cutoff for this analysis (ADM: n=110; nADM: n=188). The mortality rate due to ADM decreased from 20.1/1000 person-years of follow-up [95% confidence interval (CI) 14.4, 25.9] when the most recent CD4 cell count was <50 cells/μl to 0.1 (0.03, 0.3)/ 1000 person-years of follow-up when the CD4 cell count was more than 500 cells/μl; the mortality rate from nADM decreased from 6.0 (95% CI 3.3, 10.1) to 0.6 (0.4, 0.8) per 1000 person-years of follow-up between these two CD4 cell count strata. In multivariable regression analyses, a two-fold higher latest CD4 cell count was associated with a halving of the risk of ADM mortality. Other predictors of an increased risk of ADM mortality were homosexual risk group, older age, a previous (non-malignancy) AIDS diagnosis and earlier calendar years. Predictors of an increased risk of nADM mortality included lower CD4 cell count, older age, current/ex-smoking status, longer cumulative exposure to combination antiretroviral therapy, active hepatitis B infection and earlier calendar year. Conclusion: The severity of immunosuppression is predictive of death from both ADM and nADM in HIV-infected populations.