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Relationship Between Current Level of Immunodeficiency and Non-Acquired Immunodeficiency Syndrome-Defining Malignancies

BACKGROUND: In the combined antiretroviral therapy (cART) era, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies account for more morbidity and mortality in human immunodeficiency virus-infected patients than AIDS-defining malignancies. However, conflicting data have been reported on the relationship between immunodeficiency and the development of some non- AIDS-defining malignancies. METHODS: A total of 14, 453 patients from the prospective, multinational EuroSIDA cohort were included. Malignancies were classified as virus-related, non-virus-related epithelial, and other. The incidence of non-AIDS-defining malignancies was calculated stratified by current CD4 count. Poisson regression was used to investigate factors associated with the development of non-AIDS- defining malignancies. RESULTS: A total of 356 non-AIDS-defining malignancies occurred, with an incidence rate of 4.3 per 1000 person years of follow-up (95% confidence interval [CI], 3.8-4.7) ; 172 (48.3%) were virus-related, 135 (37.9%) were non-virus-related epithelial, and 49 (13.7%) were classified as other. Anal (69 cases), lung (31 cases), and melanoma (13 cases), respectively, were the most common non-AIDS-defining malignancies within each group. After adjustment, current CD4 was associated with virus-related non- AIDS-defining malignancies (incidence rate ratio [IRR], 0.81 per doubling ; 95% CI, 0.75-0.88 ; P < .0001) and non-virus-related epithelial non-AIDS- defining malignancies (IRR, 0.84 ; 95% CI, 0.75- 0.95 ; P = .004), but not with other non-AIDS- defining malignancies (IRR, 1.04 ; 95% CI, 0.83- 1.31 ; P = .73). Current CD4 count was also associated with anal cancer (IRR, 0.86 ; 95% CI, 0.75-0.99 ; P = .03), Hodgkin lymphoma (n = 52 ; IRR, 0.83 ; 95% CI, 0.73-0.95 ; P = .005), and lung cancer (IRR, 0.76 ; 95% CI, 0.64-0.90 ; P = .0002). CONCLUSIONS: A low current CD4 count was associated with an increased incidence of certain non-AIDS-defining malignancies. Starting cART earlier to reduce the proportion of patients with a low CD4 count may decrease the rate of developing many common non-AIDS-related malignancies. A randomized trial to explore this strategy is urgently needed. Cancer 2010 ; 116:5306-15. (c) 2010 American Cancer Society.

Acquired Immunodeficiency Syndrome/ complications; Adult; CD4 Lymphocyte Count; Female; Humans; Incidence; Male; Neoplasms/complications/ epidemiology/immunology; Risk Factors; Tumor Virus Infections/epidemiology/immunology

Group Authors: EuroSIDA.