Role of Uncontrolled HIV RNA Level and Immunodeficiency in the Occurrence of Malignancy in HIV-Infected Patients during the Combination Antiretroviral Therapy Era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort

Background. Human immunodeficiency virus (HIV)-infected patients are at higher risk of malignancies. In addition to traditional determinants, a specific deleterious effect of HIV and immunodeficiency is speculated. We aimed at studying the association between immunological and virological characteristics of HIV-infected patients in care and the risk of acquired immunodeficiency syndrome (AIDS)-defining and non-AIDS-defining malignancies. Methods. Patients consecutively enrolled in the hospital-based Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort were included if the duration of follow-up was 13 months during the period 1998-2006. Multivariate modeling used an extended Cox proportional hazards model for time-dependent covariates and delayed entry. Results. The 4194 patients included in the study developed 251 first malignancies during 22,389 person-years. A higher incidence of AIDS-defining malignancies (107 cases) was independently associated with (1) both longer and current exposures to a plasma HIV RNA level 1500 copies/mL (hazard ratio [HR], 1.27 per year [P < .001] and 3.30 [P < .001], respectively) and (2) both longer and current exposure to a CD4(+) cell count < 200 cells/mm(3) (HR, 1.36 per year [P < .001] and 6.33 [P < .001], respectively). A higher incidence of non-AIDS-defining malignancies (144 cases) was independently associated with longer and current exposure to a CD4(+) cell count < 500 cells/mm(3) (HR, 1.13 per year [P = . 01] and 2.07 [P < .001], respectively) and male sex (HR, 1.69; P = . 02) but not with plasma HIV RNA level (P = . 49 and P = . 10 for cumulative and current exposures, respectively). Conclusions. Uncontrolled plasma HIV RNA level was independently associated with a higher likelihood of developing AIDS-defining malignancies, whereas immunosuppression was associated with a higher risk of developing any type of malignancies. Antiretroviral treatment should aim at reaching and maintaining a CD4(+) count 1500 cells/mm(3) to prevent the occurrence of malignancy, this should be integrated to malignancy-prevention policies.