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Human immunodeficiency virus-associated lymphomas

Background

Overview

Definition
HIV-associated lymphomas are a group of malignancies that occur in patients with HIV infection, as they are at increased risk of both non-Hodgkin's and Hodgkin's lymphomas compared to the general population.
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Pathophysiology
HIV infection leads to immunodeficiency, which is a significant risk factor for the development of lymphomas. The virus may also directly contribute to lymphomagenesis through biologic effects mediated by HIV products that accumulate in lymphoid tissues. Oncogenic viruses, such as EBV and Kaposi sarcoma herpesvirus (also called human herpes virus 8), are often implicated in the pathogenesis of HIV-associated lymphomas.
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Epidemiology
The incidence of non-Hodgkin's lymphomas has decreased in the antiretroviral therapy era, with the following reported rates per 100,000 patients in the US and Canada: 9.6 for CNS non-Hodgkin's lymphoma, 51.3 for diffuse large B-cell lymphoma, 11.9 for Burkitt's lymphoma, 13.5 for other specified non-Hodgkin's lymphomas, and 15.8 for non-Hodgkin's lymphomas not otherwise specified. In contrast, the incidence of Hodgkin's lymphoma has increased since the introduction of antiretroviral therapy, with a reported incidence of 32.4 per 100,000 patients in the United Kingdom.
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Risk factors
The degree of immunodeficiency, as indicated by CD4 cell counts, is a significant risk factor for the development of HIV-associated lymphomas. Coinfection with oncogenic viruses, such as EBV and Kaposi sarcoma herpesvirus, is a known risk factor for the development of these lymphomas.
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Disease course
HIV-associated lymphomas often present at an advanced stage with aggressive features, extranodal disease, and sometimes involve unusual sites.
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Prognosis and risk of recurrence
The prognosis for patients with HIV-associated lymphomas has improved significantly with the introduction of combination antiretroviral therapy. In the antiretroviral therapy era, the 5-year survival rate in patients with HIV-associated lymphomas in the US is estimated at 44%.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of human immunodeficiency virus-associated lymphomas are prepared by our editorial team based on guidelines from the European Hematology Association (EHA/ESMO 2024), the European Association of Neuro-Oncology (EANO 2023), the British Society for Haematology (BSH 2016), and the British HIV Association (BHIVA 2014).
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Diagnostic investigations

Initial evaluation: as per EHA/ESMO 2024 guidelines, obtain diagnostic evaluation following recommendations for HIV-negative patients and patients with HIV requiring assessment of the severity and complications of HIV.
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  • Imaging for staging

  • CSF analysis

Medical management

Antiretroviral therapy
As per EHA/ESMO 2024 guidelines:
Continue concomitant antiretroviral therapy in patients receiving treatment for HIV-associated lymphoma.
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Consider initiating or optimizing antiretroviral therapy in patients with multicentric Castleman's disease.
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Use a multidisciplinary approach, including an HIV specialist, to prevent drug-drug interactions.
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  • Management of Hodgkin's lymphoma (early-stage disease)

  • Management of Hodgkin's lymphoma (advanced-stage disease)

  • Management of Hodgkin's lymphoma (relapsed/refractory disease)

  • Management of Hodgkin's lymphoma (monitoring)

  • Management of diffuse large-B cell lymphoma (evaluation)

  • Management of diffuse large-B cell lymphoma (initial therapy)

  • Management of diffuse large-B cell lymphoma (CNS prophylaxis)

  • Management of diffuse large-B cell lymphoma (relapsed/refractory disease)

  • Management of Burkitt's lymphoma (evaluation)

  • Management of Burkitt's lymphoma (initial therapy)

  • Management of Burkitt's lymphoma (relapsed/refractory disease)

  • Management of primary CNS lymphoma (initial therapy)

  • Management of primary CNS lymphoma (relapsed/refractory disease)

  • Management of plasmablastic lymphoma (induction therapy)

  • Management of plasmablastic lymphoma (consolidation therapy)

  • Management of plasmablastic lymphoma (relapsed/refractory disease)

  • Management of primary effusion lymphoma (evaluation)

  • Management of primary effusion lymphoma (initial therapy)

  • Management of primary effusion lymphoma (relapsed/refractory disease)

  • Management of multicentric Castleman's disease (evaluation)

  • Management of multicentric Castleman's disease (initial therapy)

  • Management of multicentric Castleman's disease (relapsed/refractory disease)

  • Management of multicentric Castleman's disease (monitoring)

Preventative measures

Infection prophylaxis
As per EHA/ESMO 2024 guidelines:
Offer prophylaxis against pneumocystis pneumonia in all patients,
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especially with a CD4 count of < 200 cells/mcL.
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Offer antiviral prophylaxis with acyclovir or valacyclovir in patients with a history of HSV or VZV infection and when the CD4 count is < 200 cells/mcL.
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