Abstract
BackgroundThe 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.MethodsWe 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.Results31,056 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/µL (IRR=1.67, 95%CI=1.16-2.40) and <200 cells/µL (IRR=1.61, 95%CI=1.09-2.39), compared to >350 cells/µL. 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.ConclusionThese 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.
Highlights
The introduction of combination anti-retroviral therapy in 1996 transformed the epidemiology of HIV infection and prolonged survival of infected individuals in the United States [1,2]
From 3-24 months after combined antiretroviral therapy (cART) initiation, different CD4 trajectories were observed between Hodgkin lymphoma (HL) cases and non-cases; non-cases continued to show slight CD4 increases while HL cases experienced declining CD4 to near cART initiation levels. This is the first study to conduct a careful analysis of cART-associated immune reconstitution on the risk of HL, exclusively among a cohort of HIV-infected veterans who had all received cART
We were able to determine that HL risk was reduced among individuals with a greater percent time undetectable HIV RNA, and that HL risk was elevated in the interval directly following cART initiation, after adjusting for nadir and recent CD4 counts
Summary
The introduction of combination anti-retroviral therapy (cART) in 1996 transformed the epidemiology of HIV infection and prolonged survival of infected individuals in the United States [1,2] During this interval, the incidence of nonAIDS-defining malignancies (NADMs) has increased [3,4,5]. There is limited research examining HIV-related immune factors and immune reconstitution associated with increased HL incidence in a cohort of individuals receiving cART. The aim of the present study was to evaluate the effect of immune reconstitution on HL incidence among a cohort of male US military veterans ever receiving cART and diagnosed with HIV infection between 1985 and 2010. 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. Findings suggest an immune reconstitution type mechanism in HIV-related HL development
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