15
Immunodeficiency and Risk of AIDS-defining and Non-AIDS-defining Cancers: ANRS CO3 Aquitaine Cohort, 1998 to 2006
M Bruyand1,2, R Thiebaut1,2,3,4, S Lawson-Ayayi1,2, P Joly3,4, A Sasco5, J L Pellegrin2,4,6, D Neau2,4,6, P Morlat1,2,4,6, G Chene1,2,4, Fabrice Bonnet*1,2,4,6, and Groupe d'Epidémiologie Clinique du SIDA en Aquitaine (GECSA)
1INSERM U593 and CIC-EC7, Bordeaux, France; 2Ctr Hosp Univ Bordeaux, France; 3INSERM U875, Bordeaux, France; 4Univ Victor Segalen, Bordeaux, France; 5INSERM U897, Bordeaux, France; and 6Ctr Hosp Univ Bordeaux, France
Background: HIV-infected
patients have a high risk of AIDS- and non-AIDS-defining cancers. Besides
traditional determinants, a specific role of HIV, immunodepression, and ART
cannot be excluded. We aimed at studying the association between the risk of
AIDS- and non-AIDS-defining cancers and either immuno-virological characteristics,
or treatment history of HIV-infected patients.
Methods: Patients from the ANRS CO3 Aquitaine Cohort were included in
the analyses if the duration of follow-up was >3 months, if they had at
least 2 follow-up visits available during the study period (1998 to 2006) and
if 1 HIV RNA viral load was collected within the first follow-up visit.
Duration of exposure was calculated as the time duration with CD4 count or
HIVRNA level above or below different thresholds. Multivariate modelling was
based on extended Cox proportional hazards models for time-dependent covariates
and delayed entry (at time of first available HIV RNA measurement).
Results: Among
the 4194 patients included, 251 cancers (109 AIDS-defining and 142
non-AIDS-defining) were reported. Regarding AIDS-defining cancers, a higher
incidence was independently associated with a longer duration of HIV RNA >500
copies/mL: relative risk (RR) = 1.20 per year of exposure (95% confidence
interval [CI] 1.10 to 1.31, p <10–3) and a longer duration
of CD4 count <200/mm3: RR = 1.35 by year of exposure (CI 1.20 to
1.53, p <10–3). A lower incidence was associated with
duration of exposure to combination ART (cART): RR = 0.82 per year (CI 0.74 to
0.91, p <10–3). Regarding non-AIDS-defining cancers, a
higher incidence was independently associated with a longer duration of CD4
count <200/mm3: RR = 1.16 per year of exposure (CI 1.03 to 1.30,
p = 0.01) or a longer duration of CD4 count <500/mm3: RR =
1.11 per year of exposure (CI 1.01 to 1.22, p = 0.02), and a lower
incidence with female gender: RR = 0.58 (CI 0.37 to 0.92, p = 0.02).
HIV RNA and cART were not associated with the risk of non-AIDS-defining
cancers.
Conclusions:
A longer exposure to uncontrolled HIV RNA was associated with a higher risk of
AIDS-defining cancers, independently of CD4 count. Moreover, prolonged
immunosuppression was associated with a higher risk of cancers of both types,
regardless of the CD4 count threshold considered. ART should aim at reaching
and maintaining the CD4 count >500/mm3 to prevent the occurrence
of all cancers, in addition to other prevention policies.
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