# Current State of AIDS-Related Malignant Lymphoma

## TL;DR

AIDS-related lymphomas are caused by viruses like EBV and KSHV, not HIV itself, and remain a major cause of death in HIV patients despite improved treatments.

## Contribution

This paper reviews the current understanding of AIDS-related lymphomas, emphasizing their viral origins and clinical management in the cART era.

## Key findings

- HIV is not tumorigenic, but co-infection with γ-herpes viruses like EBV and KSHV is a major risk factor for AIDS-related lymphomas.
- Immunodeficiency and chronic inflammation from HIV promote lymphomagenesis.
- Prognosis for AIDS-related lymphomas is similar to non-HIV cases with appropriate treatment.

## Abstract

AIDS-related malignant lymphomas (ARLs) are the lymphomas that develop in association with HIV infection. According to the introduction of combination antiretroviral therapy (cART), the life expectancy of People Living with HIV (PLWH) has markedly improved; however, approximately one-third of PLWH have passed away from the complications of malignancies, even in well-controlled PLWH. HIV itself is not tumorigenic, and most of these tumors are due to co-infection with oncogenic viruses. γ-herpes viruses (Epstein–Barr virus: EBV and Kaposi sarcoma-associated herpesvirus: KSHV) are the most significant risk factors for ARLs. Immunodeficiency, chronic inflammation, accelerated aging, and genetic instability caused by HIV infection, as well as HIV accessory molecules, are thought to promote lymphomagenesis. The prognosis of ARLs is comparable to that of non-HIV cases in the cART era. Intensive chemotherapy with autologous stem cell transplantation is also available for relapsed/refractory ARLs. Since the early stage of HIV infection has no symptoms, significant numbers of HIV-infected individuals have not noticed HIV infection until the onset of AIDS (so-called Ikinari AIDS). Since the ratio of these patients is more than 30% in Japan, hematologists should carefully consider the possibility of HIV infection in cases of lymphoma. Even in an era of cART, ARL remains a critical complication in PLWH, warranting continuous surveillance.