title: Immunodeficiency as a risk factor for non-AIDS-defining malignancies in HIV-1-infected patients receiving combination antiretroviral therapy.
abstract: BACKGROUND
  The aim of this study was to investigate the association between immunodeficiency, viremia, and non-AIDS-defining malignancies (NADM).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Cumulative exposure to CD4+ cell counts < 200 cells/mm³ during cART was associated with an increased risk of infection-related non-AIDS-defining malignancies.
authors.affiliation: HIV Monitoring Foundation, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.m.kesselring@amc.uva.nl
authors.forename: Anouk
authors.initials: A
authors.lastname: Kesselring
authors.forename: Luuk
authors.initials: L
authors.lastname: Gras
authors.forename: Colette
authors.initials: C
authors.lastname: Smit
authors.forename: Gitte
authors.initials: G
authors.lastname: van Twillert
authors.forename: Annelies
authors.initials: A
authors.lastname: Verbon
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Wit
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D005260:Female; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000276:immunology*; D009426:Netherlands / Q000453:epidemiology; D012307:Risk Factors; D013223:Statistics as Topic; D019562:Viral Load; D014766:Viremia / Q000175:diagnosis
chemical_list: D019380:Anti-HIV Agents