Urgent Call for Attention to HIV‐Associated Lymphoma: After AIDS 2024, the 25th International AIDS Conference

The 25th International AIDS Conference (AIDS 2024) was held from July 22nd to 26th, 2024, in Munich, Germany, attracting over 15 000 scientists from more than 175 countries and regions worldwide to discuss the latest advancements and future challenges in HIV research. We had been eagerly anticipating the results presented at the conference, hoping to see global data on HIV-related cancers, particularly HIV-associated lymphomas (HALs). However, with great disappointment, no reports on HALs were available. The overall focus on HIV-related cancers in the conference was relatively scarce, and the only studies on cancers were on HPV co-infection-associated cervical cancer (CC) and anal cancer, with a special focus on their early screening strategies. The countries of interest are mainly low- and middle-income countries, like Kenya and Tanzania [1]. In fact, since early ART time, lymphoma has surpassed Kaposi sarcoma (KS) as the most prevalent cancer in people living with HIV (PLWH) (supported by Figure 1a and Supporting Information S1: Table S1) [2-12]. HALs exhibit unique clinical features, such as initial diagnosis often at advanced stages, aggressive manifestations and susceptible to extranodal involvement, resulting in poor treatment outcomes [13]. In contrast, despite the clinical heterogeneity of HIV-related KS, the emergence of antiretroviral therapy (ART) has effectively restricted the disease progression [14]. With the long-term effective control of HIV, cancer has become the leading cause of deaths in developed countries, and the death percentage of HALs is the largest among all AIDS-defining cancers, which must draw our great attention (Figure 1b and Supporting Information S1: Table S2) [15-20]. Together with the two guidelines published by the National Comprehensive Cancer Network in April this year, “B-Cell Lymphoma Guideline” and “Cancer in People with HIV Guideline”, both of which describe AIDS-defining cancers in detail. However, their definitions have some discrepancies from the 2023 WHO classification. AIDS-defining malignancies in “Cancer in People with HIV Guideline” include CC, KS, PCNSL, and aggressive NHL [21]. HIV-related B-cell lymphomas include BL, PCNSL, DLBCL, HHV-8 positive DLBCL (NOS), PEL, and PBL in “B-Cell Lymphoma Guideline” [22]. But the 2023 WHO classification (5th edition), as an update 30 years later, compared to the 1993 AIDS surveillance report, excluded PCNSL from the AIDS-defining lymphomas (Table 1) [23]. So, the categorization of PCNSL varies between guidelines, and there is still some disagreement as to whether it belongs to HALs, which requires more research and attention. Due to the unclear treatment guidelines, lack of clinical trials, incompletely known side effects between anticancer and antiviral drugs, and patients' misunderstandings about this disease, the treatment of HALs faces many challenges. Additionally, factors such as severe pain, demanding nursing needs, high treatment costs, income reduction, and the stigma and shame related to this disease significantly reduce HALs patients' quality of life [24, 25]. Therefore, more support from society is needed for this group of people. CC KS PCNSL aggressive NHL BL PCNSL DLBCL HHV-8 positive DLBCL, NOS PEL PBL BL DLBCL PEL and its solid variant PBL KSHV/HHV8-positive DLBCL Intriguingly, the eight cases of HIV cure in the world (including the eighth case disclosed at HIV Glasgow 2024) were all patients with HIV-associated hematologic malignancies (acute myeloid leukemia or Hodgkin lymphoma), and all of them achieved HIV cure after receiving hematopoietic stem cell transplantation [26]. This suggests that the decoding of PLWH with hematologic malignancies may be an inevitable pathway to HIV cure, so strengthening the study of such patients is an urgent need for current research in the field of AIDS. Therefore, we strongly appeal to all walks of society to pay attention to HALs, not limited to its definition, pathogenesis, early surveillance strategies, and emerging therapy alternatives. All the authors were actively involved in the analysis and interpretation of the research study and have contributed to this letter. They all had unrestricted access to the data and provided their final approval before submission. Moreover, all the authors are willing to take responsibility for every aspect of the work. This study was supported by the Natural Science Foundation of Chongqing, China (CSTB2022NSCQ-MSX1150). The authors declare no conflicts of interest. All data sources can be obtained in the text and the supplementary materials. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.