B-cell stimulation and prolonged immune deficiency are risk factors for non-Hodgkin's lymphoma in people with AIDS

Objectives: To identify risk factors for non-Hodgkin's lymphoma (NHL) in pe ople with HIV infection. Design and setting: Case-control study in Sydney, Australia. Participants and methods: Two hundred and nineteen patients with AIDS-relat ed NHL were compared with 219 HIV-infected controls without NHL, matched fo r CD4 positive cell count and date of specimen collection. Data on demograp hic, infectious, treatment-related and immunological factors were abstracte d by medical record review. The association between demographic factors, se xually transmissible diseases, HIV-related opportunistic infections, anti-v iral therapy, duration of immune deficiency and indices of immune stimulati on and risk of NHL were derived for these groups. Results: In a multivariate model, there were two independent groups of pred ictors of NHL risk. The fi rst was du ration of immunodeficiency, as measur ed by longer ii me 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; 9 5% confidence interval (CI), 1.15-2.88]. Indices of B-cell stimulation prec eded the diagnosis of NHL by several years. Factors not related to NHL risk included clinical indices of Epstein-Barr virus infection and receipt of i ndividual nucleoside analogue antiretroviral agents. Combination therapy wi th 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 stimulat ion were associated with an increased risk of developing NHL. Unless the st rongest risk factor for NHL, immune deficiency can be reversed, NHL is like ly to become proportionately more important as a cause of morbidity and mor tality in people with HIV infection. (C) 2000 Lippincott Williams & Wilkins .