AIDS-Related Lymphomas

Updated: Dec 22, 2022
  • Author: Christina Poh, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Practice Essentials

Acquired immune deficiency syndrome (AIDS)–related lymphoma is a subset of lymphomas commonly encountered in patients infected with human immunodeficiency virus (HIV). [1] Most are aggressive lymphomas of B-cell origin [2]  and include the following subtypes [3] :

  • Non-Hodgkin lymphoma (NHL)
  • Hodgkin lymphoma (HL)
  • Primary effusion lymphoma
  • Primary central nervous system (CNS) lymphoma

AIDS-related NHLs include the following:

  • Diffuse large B-cell lymphoma (DLBCL), immunoblastic variant
  • Burkitt lymphoma
  • Plasmablastic lymphoma
  • Other lymphomas (eg, indolent B-cell lymphoma, T-cell and natural killer [NK]-cell lymphoma)


The pathogenesis of NHL development in the setting of HIV infection is not well elucidated. However, the following factors are thought to play an important role:

  • Chronic B-cell stimulation [4]
  • Cytokine dysregulation
  • Co-infection with oncogenic viruses (Epstein-Barr virus [EBV], human herpesvirus 8 [HHV-8], hepatitis B and C viruses) in the setting of immune dysregulation, resulting in decreased surveillance for tumor antigens [5, 6]
  • Genetic abnormalities (decreased BCL-2 activation and increased BCL-6 and MYC expression) [7, 8]

Different clinicopathologic categories of AIDS-related lymphomas arise from distinct B-cell subtypes, and the factors mentioned above interplay in varying proportions to give rise to different varieties of NHL.



It is estimated that 25% to 40% of patients with HIV infection will develop a malignancy and approximately 10% will develop NHL. [9]  AIDS-related lymphoma is more common in males than in females. [10] With the advent of anti-retroviral therapy (ART), the incidence rate of AIDS-defining lymphoma has substantially declined; however, it still remains substantially higher compared with the general population. [11]  A meta-analysis of over 400,000 patients showed the observed rate of lymphoma development in the HIV population to be 11.03 times that of the general population. [12]

Up to 85% of AIDS-related lymphomas are highly aggressive and include DLBCL, immunoblastic variant; and Burkitt lymphoma. Incidences and relative risks of AIDS-related lymphomas are shown in Table 1, below. [13, 14, 15, 16, 17]  

Table 1: Incidence and relative risk of AIDS-related lymphoma subtypes (Open Table in a new window)

Lymphoma subtype

Incidence (% of HIV-related lymphomas)

Relative risk (compared with the general population)

DLBCL, immunoblastic variant



Burkitt lymphoma



Indolent B-cell lymphoma

< 10


T-cell lymphoma



Hodgkin lymphoma

< 10


Primary CNS lymphoma



Plasmablastic lymphoma



Primary effusion lymphoma

< 1



Risk Factors

Risk factors for developing AIDS-related lymphoma include the following: [18]

  • Low CD4 count - A study of 52,278 patients from the French Hospital Database found CD4 cell count to be the most predictive risk factor of AIDS-related cancer incidence: Hodgkin lymphoma was 5.4 times more likely to develop in patients with CD4 cell count < 50/μL than in those with CD4 count > 500/μL. [19]
  • High HIV viral load
  • EBV co-infection
  • Genetic factors -  CCR5-32 deletion is associated with favorable prognosis, whereas CXCR-4 is associated with increased risk for NHL development [20, 21]  
  • Other undefined risk factors that increase the risk of NHL in the general population


ART can significantly affect the outcomes of AIDS-related lymphoma by reducing viral replication, and its use plays a pivotal role in improving prognosis. In addition, the prognosis of patients with AIDS-related lymphoma have been associated with the following factors: [3]

  • Stage (extent of disease, extranodal or CNS involvement)
  • Age
  • Severity of the underlying immunodeficiency (measured by CD4 cell count)
  • Performance status
  • Prior AIDS diagnosis (ie, history of opportunistic infection or Kaposi sarcoma)

An AIDS-related lymphoma International Prognostic Index (IPI) has been developed and employs the age adjusted-IPI in addition to CD4 count, viral load, and prior history of AIDS. [22] This index performed better in predicting risk of death compared to the age-adjusted IPI.

Prognosis in patients with AIDS-related lymphoma varies depending on histologic subtype. A large body of evidence indicates that HIV-infected patients whose HIV disease is well controlled with ART and are treated with standard chemotherapies for DLBCL, Burkitt lymphoma, and Hodgkin lymphoma have outcomes similar to those of their uninfected counterparts. [23]  However, a diagnosis of primary effusion lymphoma or plasmablastic lymphoma generally confers a poor prognosis. [24]