Infection with human immunodeficiency virus (HIV) is associated with substantially increased incidence of
non-Hodgkin lymphoma (NHL). This risk may be driven, in part, by reduced immune control over
viral infections in the setting of
acquired immunodeficiency syndrome (
AIDS), although the lymphomagenic mechanisms are not yet established. We used bead-based multiplex assays to measure antibody seroreactivity to 32
viral antigens representing 22 different
viral infections (human herpesviruses 1-8,
hepatitis B and C virus, human T-lymphotropic virus type-1, and human polyomaviruses) in two prospective HIV cohorts. Incident (n = 28) and prevalent (n = 38)
AIDS-related NHL cases were matched by age, sex, race, and CD4 count to 67 HIV-positive control individuals without
AIDS-NHL. Logistic regression was used to estimate odds ratios (
ORs) and 95% confidence intervals (CIs) for associations of
AIDS-NHL with the number of different viruses to which an individual was seropositive and seroreactivity to individual
antigens. Seropositivity to an increasing number of viruses was inversely associated with
AIDS-NHL (OR per virus = 0.84, 95% CI = 0.72-0.98). Seroreactivity to herpes simplex virus 2 2mgG unique
antigen (OR = 0.47; 95% CI = 0.23-0.97) and to WU polyomavirus viral
capsid protein (OR = 0.26, 95% CI = 0.10-0.65) was significantly lower in
AIDS-NHL cases compared to controls. In this evaluation of
antibodies to multiple viruses, we observed an inverse association between seropositivity to a larger number of viruses and
AIDS-NHL. While in need of further evaluation, our data raise the novel hypothesis that insufficient exposures or impaired humoral immune responses to
viral infections may be associated with
AIDS-related lymphomagenesis.