• The clinical spectrum of HIV-related NHL typically includes systemic NHL, primary CNS NHL, and pleural-effusion lymphoma (PEL).
  • Although HL is not considered an AIDS-defining illness, a marked increase is seen in HIV.
• The majority of HIV-related lymphomas are of B-cell origin. T-cell lymphomas are rare, as are primary effusion lymphomas (PELs), which lack B-, T-, and hematopoietic cell markers.
• The frequency of NHL increases with the degree of immunosuppression, particularly for CNS lymphoma. Thus, CNS lymphoma is rarely seen in developed countries where ART is available, except in socioeconomic sectors where standard of care HIV therapy is not ubiquitous.
• Though EBV is detected in essentially all primary CNS NHL and most PEL, only approximately 50% to 60% of systemic HIV-related NHL have detectable EBV.
• Patients with HIV-NHL frequently present with advanced stage III or IV disease. The majority will present with a rapidly growing mass or the development of systemic B symptoms (ie, fever, night sweats, and unexplained weight loss). The clinical presentation is dependent on the site of involvement. Extranodal involvement including the bone marrow (25%-40%), gastrointestinal tract (26%), and CNS (17%-32%) is common.
• Following the introduction of highly active antiretroviral therapy (HAART) into clinical practice, there has been a decrease in primary CNS NHL and systemic diffuse large B-cell lymphoma; however, the incidence of BL remains unchanged.
  • This decrease of incidence has primarily affected lymphomas occurring at low CD4 counts, whereas NHL occurring at higher CD4 counts has been relatively unaffected.
• Outcome for patients with HIV and NHL have improved dramatically thanks to the concurrent use of HAART, chemotherapy, and aggressive supportive care, HIV patients can now tolerate standard therapies for NHL with similar outcomes.
  • Current estimates are that 4% to 5% of all NHL deaths are related to HIV, including higher contributions in the HIV-specific subtypes: 7% of DLBCL, 33% of Burkitt, and 18% of primary CNS lymphoma. Of note, these subtypes differ in their clinical presentations, in their underlying pathogenesis, and in their response to therapy.

• Extranodal sites of disease and advanced stage occur in three-fourths of patients with AIDS-related lymphoma (ARL).
• The most common extranodal sites are the meninges, gastrointestinal tract, bone marrow, liver, and lung/pleura; unusual sites include rectum, oral cavity, heart/pericardium, common bile duct, and skin.
• NHL in AIDS patients is usually of B-cell origin with the predominant types being DLBCL and BLs, but there are also increased rates of some peripheral T-cell lymphomas (PTCLs), MZL and LPL/Waldenström macroglobulinemia (WM).
• Unique presentations of ARL include plasmablastic lymphoma of the oral cavity and primary effusion lymphoma.
• The prevalence of NHL in AIDS is 3% to 6%, and before the era of ART there were projected increased risks over time.
• The risk of lymphoma formerly was increased 60- to 650-fold among HIV-infected patients compared to the general population, but is now only 9- to 23-fold higher in the ART era.
• Severe immunodeficiency (defined by CD4 count and HIV viral load), prolonged HIV infection, older age, and transmission through sex between men are risk factors for NHL. In patients receiving ART, coinfection with HBV and HCV is associated with increased NHL.
• PTCL comprise up to 7% of all AIDS lymphoma with an increased risk for ALCL and PTCL-NOS (not otherwise specified) compared to the general population.

PCNSL

• Even with poorly controlled HIV and/or marginal performance status, consider high-dose methotrexate.

Burkitt