Immune Reconstitution and Risk of Hodgkin's Lymphoma among a Sample of HIV-Infected Male Veterans

Abstract

Abstract Purpose: In contrast to certain AIDS-defining cancers, the incidence of Hodgkin's lymphoma (HL) has increased since the introduction of combined antiretroviral therapy (cART). Although HIV-associated HL has been strongly linked to the Epstein-Barr virus, the causes for the increased incidence of HL in the cART era remain unclear. The aim of this study was to evaluate the effect of cART utilization and possible immune reconstitution inflammatory syndrome (IRIS), through monitoring the activity of immunologic measures (e.g., nadir CD4 prior to cART, recent CD4, percent of time with undetectable HIV viral load), on the incidence of HL among a sample of HIV-infected male veterans. Methods: We performed a retrospective cohort study utilizing data from the Veterans Affairs HIV Clinical Case Registry (VA-CCR) from 1985–2010. HL cases were identified using ICD-9 codes. Women were excluded due to low numbers. We also excluded individuals without identifiable CD4 or viral load measurement, no cART use, <90 days of follow-up, and prevalent HL cases occurring prior to or within 90 days of HIV diagnosis. We analyzed the relationship between immunologic measures associated with cART utilization and the incidence of HL, calculated in multivariable Poisson regression models adjusted for demographic and time-varying immunologic covariates. Results: The final sample included 31,596 cART users, contributing 288,968 person-years and 219 HL cases (IR = 76 per 100,000 person-years). In multivariable regression models, the risk of HL was higher among veterans with recent CD4 <200 copies/cell (IRR = 1.57, 95%CI = 1.05–2.34) and between 200–350 copies/cell (IRR = 1.68, 95%CI = 1.17–2.40), compared to individuals with >350 copies/cell. Also, HL risk was increased among veterans within 1 year (IRR = 2.38, 95%CI = 1.60–3.53) and 1–2 years (IRR = 1.89, 95%CI = 1.27–2.82) after cART initiation, compared to >2 years. Conclusion: Recent CD4 counts <350 copies/cell were associated with an increased risk of HL among cART users. Additionally, risk of HL was increased in the 2 years directly following cART initiation. Findings indicate an EBV-associated IRIS may function in HL development in HIV-infected individuals.