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Longer duration of exposure to immunodeficiency and detectable viremia both are risk factors for non-AIDS defining malignancies in HIV-1 infected patients on combination antiretroviral therapy
Presented by Anouk Kesselring (Netherlands).
A. Kesselring1, L. Gras1, C. Smit1, F. de Wolf1, P. Reiss2, F. Wit2
1HIV Monitoring Foundation, Amsterdam, Netherlands, 2Academic Medical Center of the University of Amsterdam, Department of Infectious Diseases, Tropical Medicine and AIDS, Amsterdam, Netherlands
Background: We aimed to investigate the association between immunodeficiency and viremia and non-AIDS defining malignancies.
Methods: We selected patients from the national observational Netherlands Athena cohort starting combination antiretroviral therapy (cART) since 1/1/1996. Cox models were used to compare the risk of fatal and non-fatal non-AIDS malignancies (NADM) according to potential risk factors such as CD4 count and viral load at start cART, region of origin, age, gender, mode of transmission, smoking, alcohol use, prior AIDS diagnosis, duration of exposure to cART and interval between HIV-1 diagnosis and start cART. CD4 count and viral load were also considered as time-updated variables, and as a measure of cumulative exposure to levels below a threshold (years with CD4 < 350 cells/mm³, years detectable viremia >50 cps/ml, respectively).
Results: In 9595 selected patients, 224 NADM were diagnosed. (35 anal, 37 lung, 7 hematological, 13 Hodgkin's lymphoma, 20 genitourinary, 34 digestive tract, 28 other and 50 unspecified). Median CD4 count at NADM diagnosis was 358 cells/mm³ (IQR 210-550). Time till first NADM after starting cART was 5.3 (2.4- 8.1) years. In univariate models both cumulative exposure to immunodeficiency < 350 cells/mm³ and current CD4 cell count were significantly associated with an increased risk of NADM. In multivariate models, cumulative exposure to CD4 count < 350 cells/mm³, but not current CD4 count remained significant, HR 1.09 (1.03-1.17, p=0.005) for each additional year of exposure. Longer exposure to detectable viremia was associated with an increased risk of NADM, HR 1.09 (1.01-1.17, p=0.02) for each additional year. Other factors independently associated with NADM were age HR 1.06 (1.05-1.08) and duration of exposure to HIV infection HR 1.04 (1.00-1.07), per year.
Conclusions: After adjusting for traditional risk factors, both longer exposure to CD4 < 350 cells/mm3 and detectable viremia during cART were associated with an increased risk of non-AIDS defining malignancies.
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