Immunodeficiency as a risk factor for non-AIDS-defining malignancies in HIV-1-infected patients receiving combination antiretroviral therapy

The aim of this study was to investigate the association between immunodeficiency, viremia, and non-AIDS-defining malignancies (NADM). Patients starting combination antiretroviral therapy (cART) as of 1 January 1996 were selected from the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. In Cox models, risk factors for NADM were investigated. These included age, sex, transmission route, smoking, alcohol abuse, prior AIDS diagnosis, duration of exposure to cART, and estimated duration of human immunodeficiency virus infection. CD4+ cell count and viral load (VL) were considered as time-updated variables and as measures of cumulative exposure to CD4+ cell counts of < 200, < 350, or < 500 cells/mm³ and detectable VL >50, >400, and >1000 copies/mL, respectively. In a cohort of 11,459 patients, 236 NADMs were diagnosed; 102 were caused by infection, and 134 were attributable to other causes. Median CD4+ cell count at NADM diagnosis was 340 cells/mm³ (range, 210-540 cells/mm³). Median time to first NADM after starting cART was 5.0 years (range, 2.2-8.2 years). In multivariate models, cumulative exposure to CD4+ cell counts < 200 cells/mm³ remained significant (hazard ratio [HR], 1.12; range, 1.03-1.22) for each additional year of exposure. In stratified analyses, cumulative exposure to CD4+ cell counts < 200 cells/mm³ was associated with malignancies possibly caused by infection (HR, 1.16; range, 1.03-1.31]) but was not associated with other types of cancers. No significant effect of viremia was seen in either type of cancer. Cumulative exposure to CD4+ cell counts < 200 cells/mm³ during cART was associated with an increased risk of infection-related non-AIDS-defining malignancies