title: Relationship between current level of immunodeficiency and non-acquired immunodeficiency syndrome-defining malignancies.
abstract: BACKGROUND
  In the combined antiretroviral therapy (cART) era, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies account for more morbidity and mortality in human immunodeficiency virus-infected patients than AIDS-defining malignancies. However, conflicting data have been reported on the relationship between immunodeficiency and the development of some non-AIDS-defining malignancies.
  
  
  METHODS
  A total of 14,453 patients from the prospective, multinational EuroSIDA cohort were included. Malignancies were classified as virus-related, non-virus-related epithelial, and other. The incidence of non-AIDS-defining malignancies was calculated stratified by current CD4 count. Poisson regression was used to investigate factors associated with the development of non-AIDS-defining malignancies.
  
  
  RESULTS
  A total of 356 non-AIDS-defining malignancies occurred, with an incidence rate of 4.3 per 1000 person years of follow-up (95% confidence interval [CI], 3.8-4.7); 172 (48.3%) were virus-related, 135 (37.9%) were non-virus-related epithelial, and 49 (13.7%) were classified as other. Anal (69 cases), lung (31 cases), and melanoma (13 cases), respectively, were the most common non-AIDS-defining malignancies within each group. After adjustment, current CD4 was associated with virus-related non-AIDS-defining malignancies (incidence rate ratio [IRR], 0.81 per doubling; 95% CI, 0.75-0.88; P < .0001) and non-virus-related epithelial non-AIDS-defining malignancies (IRR, 0.84; 95% CI, 0.75-0.95; P = .004), but not with other non-AIDS-defining malignancies (IRR, 1.04; 95% CI, 0.83-1.31; P = .73). Current CD4 count was also associated with anal cancer (IRR, 0.86; 95% CI, 0.75-0.99; P = .03), Hodgkin lymphoma (n = 52; IRR, 0.83; 95% CI, 0.73-0.95; P = .005), and lung cancer (IRR, 0.76; 95% CI, 0.64-0.90; P = .0002).
  
  
  CONCLUSIONS
  A low current CD4 count was associated with an increased incidence of certain non-AIDS-defining malignancies. Starting cART earlier to reduce the proportion of patients with a low CD4 count may decrease the rate of developing many common non-AIDS-related malignancies. A randomized trial to explore this strategy is urgently needed.
authors.affiliation: University College London Medical School, London, UK. j.reekie@pcps.ucl.ac.uk
authors.forename: Joanne
authors.initials: J
authors.lastname: Reekie
authors.forename: Csaba
authors.initials: C
authors.lastname: Kosa
authors.forename: Frederik
authors.initials: F
authors.lastname: Engsig
authors.forename: Antonella d'Arminio
authors.initials: Ad
authors.lastname: Monforte
authors.forename: Alicja
authors.initials: A
authors.lastname: Wiercinska-Drapalo
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Francisco
authors.initials: F
authors.lastname: Antunes
authors.forename: Nathan
authors.initials: N
authors.lastname: Clumeck
authors.forename: Ole
authors.initials: O
authors.lastname: Kirk
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000453:epidemiology* / Q000276:immunology; D012307:Risk Factors; D014412:Tumor Virus Infections / Q000453:epidemiology / Q000276:immunology