Several types of lymphoma are associated with HIV, but three are so closely linked that the CDC classifies them as AIDS-defining cancers: diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and primary central nervous system (CNS) lymphoma. A diagnosis of any of these in a person with HIV is enough to establish an AIDS diagnosis, regardless of their immune cell count. Beyond these three, HIV also raises the risk of Hodgkin lymphoma, primary effusion lymphoma, and plasmablastic lymphoma.
The Three AIDS-Defining Lymphomas
HIV doesn’t raise the risk of all lymphomas equally. Compared to the general population, people with HIV face a 30-fold increased risk of DLBCL, a 50-fold increased risk of Burkitt lymphoma, and a staggering 1,020-fold increased risk of primary CNS lymphoma. All three are non-Hodgkin lymphomas that arise from B cells, the white blood cells responsible for producing antibodies. HIV progressively weakens immune surveillance over these B cells, allowing them to multiply unchecked and accumulate genetic damage.
Two viruses often act as accomplices. Epstein-Barr virus (EBV), the virus behind mono, is found in the tumor cells of many HIV-related lymphomas. Human herpesvirus 8 (HHV-8) plays a role in certain rarer subtypes. Both viruses produce proteins that hijack normal cell growth controls and help infected cells dodge immune detection. In a person whose immune system is already compromised by HIV, these viral hijackers face far less resistance.
Diffuse Large B-Cell Lymphoma
DLBCL is the most common lymphoma in people with HIV. It comes in two main forms. The centroblastic variant tends to appear in people whose immune systems are still relatively intact, and EBV is present in about 25 to 30 percent of these cases. The immunoblastic variant shows up more often in people with advanced immune suppression, and EBV is found in 90 to 100 percent of those tumors. This pattern illustrates a broader principle of HIV-related cancers: the weaker the immune system, the more opportunity cancer-causing viruses have to drive tumor growth.
Even with modern antiretroviral therapy (ART), people with HIV remain about five times more likely to develop DLBCL than the general population. The good news is that incidence dropped 23 percent between the periods of 2010 to 2014 and 2015 to 2019, a trend driven by earlier HIV diagnosis and better viral suppression.
Burkitt Lymphoma
Burkitt lymphoma is an unusually fast-growing cancer. In people with HIV, it often behaves differently than it does in HIV-negative patients. It tends to show up at an advanced stage, with disease that has already spread beyond the lymph nodes into organs like the liver, bone marrow, or gastrointestinal tract. Elevated levels of lactate dehydrogenase, a blood marker of rapid cell turnover, are common at diagnosis.
One feature that sets Burkitt lymphoma apart from the other AIDS-defining lymphomas is that it can develop at relatively preserved immune function. In one study, the median CD4 count at diagnosis was 214 cells per microliter, and roughly half of patients still had counts above 200. This means it doesn’t require the deep immune collapse that primary CNS lymphoma typically does. It appears to be driven more by specific genetic errors in B cells than by sheer immune failure.
Primary CNS Lymphoma
Primary CNS lymphoma grows inside the brain or spinal cord and is almost always linked to EBV in people with HIV. It typically develops when the immune system is severely weakened. Patients often present with memory problems and seizures, and brain imaging frequently shows multifocal lesions, meaning the cancer appears in multiple spots rather than a single mass. The tumors tend to cluster around the fluid-filled ventricles deep in the brain.
Diagnosing this cancer in people with HIV can be tricky because a common brain infection called toxoplasmosis can look similar on imaging. When a brain biopsy is too risky (it carries roughly 8 percent morbidity and 3 percent mortality in this population), doctors may instead rely on a combination of criteria: a compatible brain scan, a specialized imaging study, and either a failed trial of toxoplasmosis treatment or detection of EBV DNA in spinal fluid. The availability of ART has dramatically reduced the incidence of this once-devastating cancer, since keeping the immune system functional prevents EBV from gaining a foothold in the brain.
Primary Effusion Lymphoma
Primary effusion lymphoma (PEL) is a rare but aggressive cancer driven by HHV-8. About 80 percent of cases are also co-infected with EBV. Rather than forming solid tumors, PEL typically causes fluid buildup in body cavities: around the lungs, around the heart, or in the abdomen. Some patients develop solid masses in the skin, gastrointestinal tract, or blood-forming organs, a pattern called extracavitary disease.
PEL often coexists with Kaposi sarcoma, another HHV-8-driven cancer, which can complicate both diagnosis and treatment. It remains one of the most difficult HIV-associated lymphomas to treat successfully.
Plasmablastic Lymphoma
Plasmablastic lymphoma has a strong association with HIV and most often appears as masses in the oral cavity or gastrointestinal tract. Involvement of lymph nodes alone, without extranodal disease, is rare. Bone marrow is affected in an estimated 27 to 40 percent of HIV-positive patients. Other sites include the genitourinary tract, CNS, lungs, liver, and bones.
This is one of the most aggressive HIV-associated lymphomas. Median survival is 6 to 11 months, reflecting how resistant the cancer tends to be to standard treatments.
Hodgkin Lymphoma
Although Hodgkin lymphoma is not classified as AIDS-defining, HIV raises the risk substantially. People with HIV are about 7.6 times more likely to develop Hodgkin lymphoma than the general population. One subtype, classified as “other classic Hodgkin lymphoma,” carries an 11-fold elevated risk. Even the nodular sclerosis subtype, the most common form overall, is about 5 times more frequent in people with HIV.
Unlike the AIDS-defining lymphomas, Hodgkin lymphoma risk has remained stubbornly elevated even as ART has become widespread. Between 2001 and 2019, the relative risk declined only about 9 percent per study period, a much slower improvement than the drops seen in DLBCL or Burkitt lymphoma. This elevated risk persists across all age groups and time periods studied, making Hodgkin lymphoma an increasingly important cancer to watch for in people living with HIV.
How Treatment Has Changed
Before effective ART existed, HIV-associated lymphomas were often rapidly fatal because patients couldn’t tolerate full-dose chemotherapy with a severely weakened immune system. ART changed that equation fundamentally. By restoring immune function and suppressing the virus, ART allows people with HIV to receive the same chemotherapy regimens used in HIV-negative patients.
The type of ART regimen matters during chemotherapy. In one study, patients on certain older antiviral combinations had a 1-year survival of 59 percent, while those on a different class of antivirals reached 86 percent. The difference wasn’t in cancer response (both groups achieved similar remission rates) but in overall survival, likely because some drug combinations interact poorly with chemotherapy, increasing toxicity or reducing effectiveness. Oncologists and HIV specialists now coordinate closely to choose ART regimens that minimize these interactions.
Overall, incidence rates for DLBCL, Burkitt lymphoma, and primary CNS lymphoma have all fallen significantly since the 1990s, and continue to trend downward. But people with HIV still face a meaningfully higher risk of lymphoma than the general population, making routine monitoring and early viral suppression the most powerful tools for prevention.