title: B-cell stimulation and prolonged immune deficiency are risk factors for non-Hodgkin's lymphoma in people with AIDS.
abstract: OBJECTIVE
  To identify risk factors for non-Hodgkin's lymphoma (NHL) in people with HIV infection.
  
  
  METHODS
  Case-control study in Sydney, Australia.
  
  
  METHODS
  Two hundred and nineteen patients with AIDS-related NHL were compared with 219 HIV-infected controls without NHL, matched for CD4 positive cell count and date of specimen collection. Data on demographic, infectious, treatment-related and immunological factors were abstracted by medical record review. The association between demographic factors, sexually transmissible diseases, HIV-related opportunistic infections, anti-viral therapy, duration of immune deficiency and indices of immune stimulation and risk of NHL were derived for these groups.
  
  
  RESULTS
  In a multivariate model, there were two independent groups of predictors of NHL risk. The first was duration of immunodeficiency, as measured by longer time since seroconversion (P for trend 0.008), and lower CD4 positive cell count 1 year prior to the time of NHL diagnosis (P for trend 0.009). The second predictor was B-cell stimulation, as indicated by higher serum globulin (a surrogate marker for serum immunoglobulin, P for trend 0.044) and HIV p24 antigenaemia [odds ratio (OR) for p24 positivity, 1.82; 95% confidence interval (CI), 1.15-2.88]. Indices of B-cell stimulation preceded the diagnosis of NHL by several years. Factors not related to NHL risk included clinical indices of Epstein-Barr virus infection and receipt of individual nucleoside analogue antiretroviral agents. Combination therapy with these agents was associated with a non-significant reduction in NHL risk (OR, 0.68; 95% CI, 0.39-1.18).
  
  
  CONCLUSIONS
  Markers of long-standing immune deficiency and B-cell stimulation were associated with an increased risk of developing NHL. Unless the strongest risk factor for NHL, immune deficiency, can be reversed, NHL is likely to become proportionately more important as a cause of morbidity and mortality in people with HIV infection.
authors.affiliation: National Centre in HIV Epidemiology and Clinical Research, Sydney, New South Wales, Australia. agrulich@nchecr.unsw.edu.au
authors.forename: A E
authors.initials: AE
authors.lastname: Grulich
authors.forename: X
authors.initials: X
authors.lastname: Wan
authors.forename: M G
authors.initials: MG
authors.lastname: Law
authors.forename: S T
authors.initials: ST
authors.lastname: Milliken
authors.forename: C R
authors.initials: CR
authors.lastname: Lewis
authors.forename: R J
authors.initials: RJ
authors.lastname: Garsia
authors.forename: J
authors.initials: J
authors.lastname: Gold
authors.forename: R J
authors.initials: RJ
authors.lastname: Finlayson
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
authors.forename: J M
authors.initials: JM
authors.lastname: Kaldor
mesh_terms: D000328:Adult; D001315:Australia / Q000453:epidemiology; D001402:B-Lymphocytes / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D016483:Lymphoma, AIDS-Related / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012712:Serum Globulins / Q000032:analysis
chemical_list: D016655:HIV Core Protein p24; D007074:Immunoglobulin G; D012712:Serum Globulins