Effect of immune reconstitution on the incidence of HIV-related Hodgkin lymphoma

• Published in: PloS one 2013-10, Vol.8 (10), p.e77409
• Main Authors: Kowalkowski, Marc A, Mims, Martha P, Amiran, E Susan, Lulla, Premal, Chiao, Elizabeth Y
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Anti-HIV Agents - adverse effects; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiretroviral Therapy, Highly Active; Biomarkers; Cancer; CD4 antigen; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD4-Positive T-Lymphocytes - virology; Comorbidity; Complications and side effects; Development and progression; Drug therapy; Epidemiology; Genetic aspects; Health services; HIV; HIV infections; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; Hodgkin Disease - chemically induced; Hodgkin Disease - epidemiology; Hodgkin Disease - immunology; Hodgkin Disease - virology; Hodgkin's disease; Hodgkin's lymphoma; Human immunodeficiency virus; Humans; Immune reconstitution; Immune response; Immunosuppression; Incidence; Laboratories; Lymphoma; Male; Medical diagnosis; Medicine; Middle Aged; Pharmacy; Physiological aspects; Poisson density functions; R&D; Registries; Research & development; Retrospective Studies; Ribonucleic acid; Risk Factors; Risk management; RNA; Statistical analysis; Studies; United States - epidemiology; Veterans; Viral Load - drug effects; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0077409

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. 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. 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 (p80% 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 36 months. 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.