Effect of Immune Reconstitution on the Incidence of HIV-Related Hodgkin Lymphoma

Background: The incidence of Hodgkin lymphoma (HL) has increased since introduction of combined antiretroviral therapy (cART). While HIV-related HL is highly associated with EBV, the causes underlying the rising incidence remain unclear. The aim of this study was to evaluate the effect of immune reconstitution on HL incidence among a cohort of HIV-infected male veterans ever receiving cART. Methods: We performed a retrospective cohort study utilizing data from the Veterans Affairs HIV Clinical Case Registry from 1985-2010. HL cases were identified using ICD-9 codes (201.4-9). Poisson regression was conducted to evaluate relationships between cART-related immunologic measures (e.g., nadir CD4 before cART, time-updated CD4, % time undetectable HIV RNA) and HL incidence. Additionally, we examined CD4 change after cART initiation. Results: 31,056 cART users contributed 287,256 person-years and 196 HL cases (IR=6.8/10,000 person-years). Rate of CD4 increase after cART was worse among HL cases than non-cases (p<0.05). In multivariate regression, HL risk was elevated among veterans with recent CD4 200-350 cells/mu L (IRR=1.67, 95% CI=1.16-2.40) and <200 cells/mu L (IRR=1.61, 95% CI=1.09-2.39), compared to >350 cells/mu L. HL risk was lower among veterans with >80% time undetectable HIV RNA (IRR=0.57, 95% CI=0.35-0.92) and 40-80% undetectable (IRR=0.68, 95% CI=0.47-0.99), compared to <40% undetectable. HL risk was higher in the first 12 months (IRR=2.02, 95% CI=1.32-3.10) and 12-24 months (IRR=1.75, 95% CI=1.16-2.64) after cART initiation, compared to >36 months. Conclusion: These data highlight immunosuppression and poor viral control may increase HL risk, specifically during immune reconstitution in the interval post cART initiation. Findings suggest an immune reconstitution type mechanism in HIV-related HL development.