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Review Highlights Progress and Challenges in Treating HIV/AIDS-Associated Lymphoma


Significant progress has led to improved survival in patients with HIV/AIDS, but lymphoma remains a leading cause of morbidity and mortality in this patient population.

Individuals with HIV or AIDS are at an increased risk for hematologic malignancies such as lymphoma. Although survival has improved in patients with HIV/AIDS since the advent of highly active antiretroviral therapy (HAART), cancer, including lymphomas, is still a leading cause of morbidity and mortality. A recent review summarized the most updated research surrounding lymphoma in patients with HIV/AIDS.

There are multiple subtypes of lymphoma associated with HIV/AIDS, the main 2 of which are non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL). NHLs are the most common HIV-related cause of death in developed countries, and they account for an estimated 23% to 30% of AIDS-related deaths. AIDS-associated NHL is more aggressive than NHLs in the general population.

Early diagnosis of lymphoma in individuals with HIV/AIDS is crucial, meaning a clear understanding of the pathophysiology, subtypes, epidemiology, laboratory diagnosis, and treatment lymphoma is important to improve outcomes further in this population.

Based on the immune status of patients with HIV, malignancies are classified as either AIDS-defining or non-AIDS-defining cancers. Common subtypes of NHLs associated with AIDS include Burkitt’s lymphoma, diffuse large cell lymphoma, primary central nervous system lymphoma, plasmablastic lymphoma, and primary effusion lymphoma (PEL). PEL is caused by HHV8, or Kaposi sarcoma-associated herpesvirus (KSHV).

HL is one of the most prevalent non-AIDS-defining cancers, and it has become increasingly common as HAART therapy has extended survival in patients with HIV. Like NHL, HL is more aggressive in patients with HIV than in the general population and has a poor prognosis. It is stratified into 2 types: classical Hodgkin lymphoma (CHL)—which accounts for more than 90% of HL cases—and nodular lymphocyte-predominant HL. Subtypes of CHL include nodular sclerosis CHL, mixed cellularity CHL, and lymphocyte-depleted CHL.

Lymphoma associated with HIV/AIDS has several potentially causal factors, including patients’ impaired immune systems, genetic alterations, viral infections, and chronic B cell activation. The increased cancer prevalence in HIV/AIDS patients in general is related to chronic antigenic stimulation, inflammation, and cytokine dysregulation.

Before HAART, patients with HIV were at a 5- to 10-times greater risk of HL and an estimated 60- to 200-times greater risk of NHL. Most types of NHL and KS have seen declining rates since the advent of HAART, which increases immune function and reduces the risk of HIV transforming into AIDS. The incidence of HL, however, has stayed consistent or increased in HIV-positive patients since the availability of HAART. More research is needed to determine the mechanisms behind this increase and the best course for treatment. Overall, study authors note that cancer screening in patients with HIV/AIDS is still crucial, even in the HAART era.

The treatment of lymphoma associated with HIV/AIDS has evolved for the better in the HAART era yet can still be challenging. In general, patients with HIV/AIDS have had good responses to chemotherapy, but the authors note that the best first-line treatment for HIV-related lymphoma is not yet clear. Therapy selection should consider the lymphoma subtype and stage, international prognostic index, performance status, and any comorbidities. However, HAART’s effect on immune function leads to a lower risk of infection and improved chemotherapy administration compared with pre-HAART era lymphoma treatment for HIV/AIDS patients.

The authors conclude that early lymphoma detection and early determination of lymphoma etiology are of the utmost importance and can significantly impact therapeutic decision-making in a positive way. The most significant revelations include the lack of improvement in HL despite advances in the HAART era and the lack of a clear best treatment for lymphoma in the HIV/AIDS patient population.

“Therefore, it is recommended that people living with HIV/AIDS be screened for the development of lymphoma to increase their survival time and quality of life,” they wrote, “and further research is required regarding the pathogenesis, treatment, and laboratory diagnosis of HIV/AIDS-associated lymphoma.”


Berhan A, Bayleyegn B, Getaneh Z. HIV/AIDS Associated Lymphoma: Review. Blood Lymphat Cancer. Published online Apr 29, 2022. doi:10.2147/BLCTT.S361320

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