The epidemiology of hodgkin lymphoma among HIV infected male US military veterans in the combined antiretroviral therapy era
Background: The incidence of Hodgkin lymphoma (HL) has increased since introduction of combined antiretroviral therapy (cART). While HIV-related HL is highly associated with Epstein-Barr virus (EBV), the causes underlying the rising incidence remain unclear. The aim of this study was to evaluate the individual effects of the duration and class of cART use, immune reconstitution, and cumulative HIV burden 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. Regression models were constructed to evaluate relationships between cART use, cART-related immunologic measures, and cumulative HIV burden and HL incidence. Results: 31,576 cART users contributed 211 HL cases. Each additional year of cART was associated with decreased HL incidence (IRR=0.80; 95%CI=0.75-0.86); results were similar for individual classes of cART use. HL risk was elevated among veterans with recent CD4 200-350 cells/ìL (IRR=1.69, 95%CI=1.17-2.42) and <200 cells>/μL (IRR=1.63, 95%CI=1.10-2.41), compared to >350 cells/μL. HL risk was also higher in the first 12 months (IRR=2.02, 95%CI=1.32-3.11) and 12-24 months (IRR=1.75, 95%CI=1.16-2.64) after cART initiation, compared to >36 months. Each log-10 increase in cumulative HIV copy-years viremia was associated with elevated HL hazard (HR=1.22; 95%CI=1.06-1.40). Conclusion: Our findings indicate class of cART use was not associated with HL development. Additionally, results demonstrate cumulative HIV exposure was associated with increased HL risk and support early cART initiation, before immune status declines, to reduce cumulative HIV burden and limit the proliferation of other oncogenic viruses (e.g., EBV). HL risk was elevated in the first 2 years directly following cART initiation, implicating a potential immune reconstitution mechanism. Therefore, individuals should be monitored rigorously during this interval, particularly individuals who do not experience a complete immunologic and virologic response following treatment. Additional research is needed to further evaluate the interaction between early cART use, EBV replication, immune reconstitution, and HL development and to define implementation strategies for cumulative HIV measurements as a screening tool for virally-mediated cancers associated with chronic HIV infection.
Kowalkowski, Marc, "The epidemiology of hodgkin lymphoma among HIV infected male US military veterans in the combined antiretroviral therapy era" (2013). Texas Medical Center Dissertations (via ProQuest). AAI3606034.