Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Oct 2;8(10):e77409.
doi: 10.1371/journal.pone.0077409. eCollection 2013.

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

Marc A Kowalkowski  1 , Martha P Mims, E Susan Amiran, Premal Lulla, Elizabeth Y Chiao
Affiliations

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

Marc A Kowalkowski et al. PLoS One. .

Abstract

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/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.

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Flow chart of selection criteria to generate final cohort of HIV-infected veterans.
Figure 2
Figure 2. Change in CD4 count after cART initiation stratified by Hodgkin lymphoma (HL) status.
Note: Hodgkin Lymphoma (HL) cases diagnosed after 24 months of cART initiation were included to avoid capturing CD4 change secondary to undiagnosed HL. Dotted lines show standard error.
Figure 3
Figure 3. Change in CD4 count after cART initiation in groups of HIV-infected individuals with different percent time undetectable HIV RNA (a) Individuals with >80% time undetectable HIV RNA (b) Individuals with 40-80% time undetectable HIV RNA (c) Individuals with <40% time undetectable HIV RNA.
Note: Hodgkin Lymphoma (HL) cases diagnosed after 24 months of cART initiation were included to avoid capturing CD4 change secondary to undiagnosed HL. Dotted lines show standard error.
See this image and copyright information in PMC

References

    1. Clifford GM, Polesel J, Rickenbach M, Dal Maso L, Keiser O et al. (2005) Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst 97(6): 425-432. doi: 10.1093/jnci/dji072. PubMed: 15770006. - DOI - PubMed
    1. Kaplan JE, Hanson D, Dworkin MS, Frederick T, Bertolli J et al. (2000) Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis 30: S5-14. doi: 10.1086/313843. PubMed: 10770911. - DOI - PubMed
    1. Herida M, Mary-Krause M, Kaphan R, Cadranel J, Poizot-Martin I et al. (2003) Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients. J Clin Oncol 21(18): 3447-3453. doi: 10.1200/JCO.2003.01.096. PubMed: 12972519. - DOI - PubMed
    1. Engels EA, Pfeiffer RM, Goedert JJ, Virgo P, McNeel TS et al. (2006) Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS 20(12): 1645-1654. doi: 10.1097/01.aids.0000238411.75324.59. PubMed: 16868446. - DOI - PubMed
    1. Shiels MS, Pfeiffer RM, Gail MH, Hall HI, Li J et al. (2011) Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst 103(9): 753-762. doi: 10.1093/jnci/djr076. PubMed: 21483021. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances