{"entity":{"id":"hiv-associated-lymphoma","kind":"cancer","name":"HIV-associated (AIDS-related) lymphomas","aka":["AIDS-related lymphoma","ARL","Primary effusion lymphoma","Plasmablastic lymphoma","HIV-associated Hodgkin lymphoma"],"tldr":"People living with HIV have a raised risk of aggressive lymphomas, driven by immune suppression and viruses such as Epstein-Barr virus. The transformation of the last two decades is that, with antiretroviral therapy continued through treatment, these lymphomas are treated with the same full-dose chemotherapy and antibody regimens as in anyone else, with similar chances of cure.","summary":"HIV-associated lymphomas are mostly aggressive B-cell lymphomas: diffuse large B-cell lymphoma (including immunoblastic and CNS variants), Burkitt lymphoma, and two entities almost specific to immunosuppression, primary effusion lymphoma (HHV-8-driven, presenting as effusions without a mass) and plasmablastic lymphoma (EBV-associated, often oral). Primary CNS lymphoma in HIV is uniformly EBV-positive and occurs at very low CD4 counts. Classical Hodgkin lymphoma is also several-fold more common in people with HIV and, unlike NHL, its incidence has not declined with antiretroviral therapy. Pathogenesis combines loss of immune surveillance of EBV and HHV-8, chronic B-cell activation, and the same oncogenic events seen in immunocompetent patients (MYC translocations in Burkitt, BCL6 rearrangements).\n\nThe pre-1996 approach of dose-reduced chemotherapy has been replaced by full-dose, curative-intent therapy alongside antiretroviral therapy, with attention to drug interactions (ritonavir- and cobicistat-boosted regimens interfere with vinca alkaloids and other agents) and infection prophylaxis. The AIDS Malignancy Consortium (AMC) trials established that rituximab is safe and beneficial when CD4 counts exceed 50 cells per microlitre (AMC 034), that R-CHOP or dose-adjusted EPOCH-R cures HIV-associated DLBCL at rates approaching those in HIV-negative patients, and that intensive Burkitt regimens or DA-EPOCH-R are effective in HIV-associated Burkitt lymphoma. Autologous transplant for relapse is feasible (BMT CTN 0803 / AMC 071), and CAR-T therapy has been given safely to people with HIV in case series and is now permitted in most CAR-T trials, reversing decades of routine exclusion. Hodgkin lymphoma is treated with ABVD or brentuximab-based regimens as in the general population.\n\nThe open fronts are HHV-8-driven disease (primary effusion lymphoma and multicentric Castleman disease, where response to standard chemotherapy is poor and pomalidomide and anti-IL-6 approaches are studied), the plasmablastic lymphoma subset (bortezomib-containing regimens, daratumumab), CNS lymphoma at low CD4 counts, and access in sub-Saharan Africa where most HIV-associated lymphoma now occurs.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/AIDS-related_lymphoma","links":[{"label":"NCI PDQ: AIDS-related lymphoma","url":"https://www.cancer.gov/types/lymphoma/patient/aids-related-treatment-pdq"},{"label":"AMC 034: rituximab plus EPOCH in HIV-associated lymphoma (Blood 2010)","url":"https://doi.org/10.1182/blood-2009-08-231613"},{"label":"NCCN: B-Cell Lymphomas (AIDS-related)","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"},{"label":"AIDS Malignancy Consortium","url":"https://amcoperations.com/"}],"tags":["nci-coverage","rare","haematologic","virus-associated"],"related":["dlbcl","burkitt-lymphoma","primary-cns-lymphoma","hodgkin-lymphoma","kaposi-sarcoma","post-transplant-lymphoproliferative-disorder"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","monoclonal-antibody","car-t","autologous-stem-cell-transplant","bispecific-antibody","global-oncology-access"],"targets":["cd20","cd19","cd30","cd38"],"drugs":["rituximab","cyclophosphamide","doxorubicin","vincristine","etoposide","methotrexate","bortezomib","daratumumab","pomalidomide","brentuximab-vedotin","axicabtagene-ciloleucel","glofitamab","epcoritamab"],"companies":[],"institutions":[],"pathways":["oncogenic-viruses","myc","antigen-presentation-immunoediting"],"terms":["ebv-term","double-hit-lymphoma","cell-of-origin","intrathecal-therapy","hhv8-kshv"],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-global-access"],"keyPapers":["paper-sparano-blood"],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Lymphoma is the most common AIDS-defining cancer in the antiretroviral era; incidence has fallen many-fold since 1996 but remains several times higher than in the general population, and Hodgkin lymphoma incidence in people with HIV has not fallen (NCI; CDC).","subtypes":["Diffuse large B-cell lymphoma (including immunoblastic)","Burkitt lymphoma","Primary effusion lymphoma (HHV-8)","Plasmablastic lymphoma (EBV, MYC)","Primary CNS lymphoma in HIV (EBV-positive)","Classical Hodgkin lymphoma in HIV","Polymorphic lymphoproliferative disorders resembling PTLD"],"biomarkers":["CD4 count and HIV viral load at diagnosis","EBV (EBER) and HHV-8 (LANA) in tumour tissue","CD20 expression (rituximab eligibility; absent in plasmablastic and often in PEL)","MYC, BCL2, BCL6 rearrangements (Burkitt vs double-hit)","CSF EBV DNA and cytology (CNS involvement)","Antiretroviral regimen and interaction profile"],"standardOfCare":[{"setting":"HIV-associated DLBCL","approach":"R-CHOP or dose-adjusted EPOCH-R at full dose with concurrent antiretroviral therapy (avoiding boosted protease inhibitors or cobicistat where possible), G-CSF support and opportunistic-infection prophylaxis; CNS prophylaxis by risk.","refs":["rituximab","cyclophosphamide","doxorubicin","vincristine","etoposide","g-csf-growth-factors"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: B-Cell Lymphomas (AIDS-related B-cell lymphomas); AMC 034 (Blood 2010)","url":"https://doi.org/10.1182/blood-2009-08-231613"}},{"setting":"HIV-associated Burkitt lymphoma","approach":"Intensive Burkitt regimens (CODOX-M/IVAC with rituximab) in fit patients, or DA-EPOCH-R (low-intensity variant studied in HIV); intrathecal prophylaxis.","refs":["rituximab","methotrexate","cyclophosphamide","etoposide"],"guideline":{"version":"NCCN Guidelines: B-Cell Lymphomas"}},{"setting":"Primary effusion and plasmablastic lymphoma","approach":"CHOP or EPOCH-based chemotherapy with antiretroviral therapy; bortezomib-containing regimens for plasmablastic; clinical trials (pomalidomide, daratumumab, anti-IL-6).","refs":["bortezomib","daratumumab","pomalidomide","etoposide"]},{"setting":"Relapsed or refractory","approach":"Salvage chemotherapy and autologous transplant (feasible with controlled HIV; BMT CTN 0803); CD19 CAR-T on the same criteria as HIV-negative patients; bispecific antibodies emerging.","refs":["autologous-stem-cell-transplant","axicabtagene-ciloleucel","car-t","glofitamab","epcoritamab","bmt-ctn-0803"]},{"setting":"HIV-associated Hodgkin lymphoma","approach":"ABVD or brentuximab-based regimens as for the general population, with antiretroviral therapy.","refs":["brentuximab-vedotin","doxorubicin","bleomycin"]}],"stateOfArt":["Full-dose immunochemotherapy with antiretroviral therapy gives cure rates approaching those in HIV-negative patients; the era of dose reduction is over.","Rituximab, once feared for infection risk, is standard when CD4 counts exceed 50, on the basis of AMC 034.","Autologous transplant and CAR-T are feasible in people with HIV; the NCI and FDA have pushed to end blanket exclusion of people with HIV from cancer trials.","The unsolved entities are HHV-8-driven and plasmablastic lymphomas and CNS lymphoma at very low CD4 counts; the AMC runs dedicated trials."],"history":[{"year":1982,"title":"Lymphoma recognised as an AIDS-defining illness","note":"Aggressive B-cell lymphoma in young men with AIDS reported; added to the CDC case definition in 1985.","refs":[]},{"year":1989,"title":"HHV-8 and EBV linked to AIDS lymphomas","note":"EBV in CNS lymphoma; HHV-8 (KSHV) identified in 1994 and linked to primary effusion lymphoma in 1995.","refs":["ebv-term"]},{"year":1996,"title":"Combination antiretroviral therapy","note":"Incidence of AIDS-related NHL falls sharply; survival after lymphoma improves as immune function is preserved.","refs":[]},{"year":2005,"title":"Rituximab controversy","note":"AMC 010 shows excess infection deaths with rituximab at very low CD4; later analyses restrict the risk to CD4 under 50.","refs":["rituximab"]},{"year":2010,"title":"AMC 034: rituximab with EPOCH is safe and effective","note":"Sparano and colleagues (Blood 2010) establish concurrent R-EPOCH.","refs":["rituximab","etoposide"]},{"year":2019,"title":"Autologous transplant in HIV lymphoma (BMT CTN 0803 / AMC 071)","note":"Outcomes comparable to HIV-negative controls.","refs":["autologous-stem-cell-transplant"]},{"year":2021,"title":"CAR-T therapy in people with HIV","note":"Case series and the AMC-sponsored study show safety; trial eligibility broadened.","refs":["car-t"]}],"pipeline":["car-t","glofitamab","epcoritamab","daratumumab","pomalidomide"],"openProblems":["Primary effusion lymphoma and multicentric Castleman disease respond poorly to chemotherapy; pomalidomide, anti-IL-6 and HHV-8-directed approaches are in AMC trials.","Plasmablastic lymphoma lacks CD20 and relapses early; bortezomib and daratumumab combinations are being tested.","CNS lymphoma at low CD4 counts remains hard to cure; high-dose methotrexate with antiretroviral therapy is now the approach rather than radiotherapy alone.","Most HIV-associated lymphoma now occurs in sub-Saharan Africa with limited access to rituximab, pathology and supportive care; global oncology programmes are the response."],"parent":"non-hodgkin-lymphoma"},"route":"/cancers/hiv-associated-lymphoma/","neighbours":{"cancer":[{"id":"burkitt-leukaemia","kind":"cancer","name":"Burkitt leukaemia","route":"/cancers/burkitt-leukaemia/"},{"id":"burkitt-lymphoma","kind":"cancer","name":"Burkitt lymphoma","route":"/cancers/burkitt-lymphoma/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"ebv-positive-dlbcl","kind":"cancer","name":"EBV-positive diffuse large B-cell lymphoma","route":"/cancers/ebv-positive-dlbcl/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"intravascular-large-b-cell-lymphoma","kind":"cancer","name":"Intravascular large B-cell lymphoma","route":"/cancers/intravascular-large-b-cell-lymphoma/"},{"id":"kaposi-sarcoma","kind":"cancer","name":"Kaposi sarcoma","route":"/cancers/kaposi-sarcoma/"},{"id":"lymphomatoid-granulomatosis","kind":"cancer","name":"Lymphomatoid granulomatosis","route":"/cancers/lymphomatoid-granulomatosis/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"plasmablastic-lymphoma","kind":"cancer","name":"Plasmablastic lymphoma","route":"/cancers/plasmablastic-lymphoma/"},{"id":"post-transplant-lymphoproliferative-disorder","kind":"cancer","name":"Post-transplant lymphoproliferative disorder (PTLD)","route":"/cancers/post-transplant-lymphoproliferative-disorder/"},{"id":"primary-cns-lymphoma","kind":"cancer","name":"Primary CNS lymphoma","route":"/cancers/primary-cns-lymphoma/"},{"id":"primary-effusion-lymphoma","kind":"cancer","name":"Primary effusion lymphoma","route":"/cancers/primary-effusion-lymphoma/"},{"id":"primary-mediastinal-b-cell-lymphoma","kind":"cancer","name":"Primary mediastinal (thymic) large B-cell lymphoma","route":"/cancers/primary-mediastinal-b-cell-lymphoma/"}],"technology":[{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"global-oncology-access","kind":"technology","name":"Global oncology and access in low- and middle-income countries","route":"/technologies/global-oncology-access/"},{"id":"g-csf-growth-factors","kind":"technology","name":"Growth factors: G-CSF and febrile neutropenia prevention","route":"/technologies/g-csf-growth-factors/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"target":[{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"},{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"},{"id":"cd30","kind":"target","name":"CD30","route":"/targets/cd30/"},{"id":"cd38","kind":"target","name":"CD38","route":"/targets/cd38/"}],"drug":[{"id":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/"},{"id":"bleomycin","kind":"drug","name":"Bleomycin","route":"/drugs/bleomycin/"},{"id":"bortezomib","kind":"drug","name":"Bortezomib","route":"/drugs/bortezomib/"},{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"epcoritamab","kind":"drug","name":"Epcoritamab","route":"/drugs/epcoritamab/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"glofitamab","kind":"drug","name":"Glofitamab","route":"/drugs/glofitamab/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"pomalidomide","kind":"drug","name":"Pomalidomide","route":"/drugs/pomalidomide/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"},{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"},{"id":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","route":"/pathways/oncogenic-viruses/"}],"term":[{"id":"cell-of-origin","kind":"term","name":"Cell of origin (GCB vs ABC)","route":"/terms/cell-of-origin/"},{"id":"double-hit-lymphoma","kind":"term","name":"Double-hit / high-grade B-cell lymphoma","route":"/terms/double-hit-lymphoma/"},{"id":"ebv-term","kind":"term","name":"Epstein-Barr virus (EBV) in cancer","route":"/terms/ebv-term/"},{"id":"hhv8-kshv","kind":"term","name":"HHV-8 (KSHV) status and LANA-1 immunohistochemistry","route":"/terms/hhv8-kshv/"},{"id":"intrathecal-therapy","kind":"term","name":"Intrathecal therapy (lumbar puncture, Ommaya reservoir)","route":"/terms/intrathecal-therapy/"}],"bottleneck":[{"id":"b-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/"},{"id":"b-trial-diversity","kind":"bottleneck","name":"Trials do not represent the people who get cancer","route":"/bottlenecks/b-trial-diversity/"}],"paper":[{"id":"paper-bmt-ctn-0803-autologous-transplant-hiv-lymphoma-alvarnas-blood-2016","kind":"paper","name":"BMT CTN 0803/AMC 071: autologous haematopoietic cell transplantation for HIV-related lymphoma","route":"/key-papers/paper-bmt-ctn-0803-autologous-transplant-hiv-lymphoma-alvarnas-blood-2016/"},{"id":"paper-sparano-blood","kind":"paper","name":"Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma","route":"/key-papers/paper-sparano-blood/"}],"trial":[{"id":"bmt-ctn-0803","kind":"trial","name":"BMT CTN 0803","route":"/trials/bmt-ctn-0803/"}]}}