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HIV-induced Immunodeficiency and Risk of Fatal AIDS-defining and Non-AIDS-defining Malignancies: Results from the D:A:D Study
Antonella D'Arminio Monforte*1, D Abrams2, C Pradier3, R Weber4, F Bonnet5, S De Wit6, N Friis-Møller7, A Phillips8, C Sabin8, J Lundgren7, and The D:A:D Study Group
1ICONA, Hosp San Paolo, Univ of Milan, Italy; 2Cancer Res Inst, Univ of California, San Francisco, US; 3Nice Cohort, Ctr Hosp Univ Nice, Hosp de l'Archet, France; 4Swiss HIV Corhort Study, Univ Hosp Zuric; 5INSERM E0338 & U593, ISPED, Univ Victor Segalen Bordeaux 2, France; 6Ctr Hosp Univ St Pierre, Brussels, Belgium; 7Copenhagen HIV Prgm, Hvidovre Univ Hosp, Denmark; and 8Royal Free Ctr for HIV Med, Royal Free and Univ Coll London, UK
Background: Immunodeficiency
increases the risk of fatal AIDS-defining malignancies (ADM),
whereas it is unclear the extent to which immunodeficiency, HIV itself, or
other factors related to the HIV infection influences the risk of non-ADM (nADM).
Methods: Risk
factors for fatal ADM and nADM were identified using
multivariable Poisson regression analyses in the D:A:D
study, a collaboration of 11 cohorts providing data on 23,441 HIV-infected
persons (76,893 person-years of prospective follow-up) seen since 1999. A
standardized and centralized procedure was used for the classification of
causes of death.
Results: Of the
total 1246 deaths (rate: 16.2/1000 person-years), 193 (1.8/1000 person-years),
and 112 (1.1/1000 person-years) were due to fatal nADM
and ADM, respectively. The 4 most frequently affected organs with nADM were the lungs (n
= 62), gastrointestinal tract (n =
41), hematological system (n = 20), and anal canal (n
= 20). The median CD4 count (percentage with HIV RNA <400 copies/mL) at death were 75 cells/µL (40%) and 211 (56%) for ADM
and nADM, respectively; >95% had been on ART and
60 to 70% were on ART at time of death. The relative risk (RR) of either nADM or ADM with a fatal outcome gradually increased with
lower latest CD4 counts (table). Conversely, latest levels of HIV RNA did not
predict risk of either type of malignancy. For fatal nADM,
older age (relative rate 1.53/5 years older; p <0.0001), current smoking (2.42; p <0.0001; not significant if lung cancers were excluded), and
active hepatitis B virus infection (1.89; p
= 0.008; not significant if hepatocellular cancer was
excluded) increased the risk; for ADM, only a prior non-fatal and non-neoplastic AIDS event increased the risk (2.43; p <0.0001). The relationship with CD4
count remained significant when only lung cancers were considered.
Conclusions: Fatal nADM are now more common than fatal ADM in contemporary
populations with access to ART, and the incidence of fatal nADM
will likely continue to increase as the HIV-infected population ages. Levels of
HIV RNA did not influence risk of fatality from either type of malignancy,
whereas immunodeficiency markedly increased risk of dying from both types of
malignancies. Hence, prevention of development of advanced immunodeficiency and
continued focus on reducing known risk factors (including smoking cessation and
treatment of chronic hepatitis B virus infection) appear to be key strategies
to prevent fatalities caused by malignancies in HIV-infected populations.
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