Advance aggressive clinical features may associate with immune dysfunction in patients with HIV positive HL in the cART era: A multicenter study from China

Xiping Liang¹Chaoyu Wang¹Yifeng Tang¹Xiaoqing Xie¹Yan Wu^2,3Haiyan Min⁴Wei Zhang⁵Wenwen Zhou¹VISHNU PRASAD ADHIKARI⁶Xiaomei Zhang¹Yao Liu^1*

• ¹Cancer Hospital, Chongqing University, Chongqing, China
• ²Henan infectious disease hospital, zhengzhou, China
• ³The Sixth People's Hospital of zhengzhou, zhengzhou, China
• ⁴Yunnan Provincial Infectious Diseases Hospital, kunming, China
• ⁵Peking Union Medical College Hospital, beijing, China
• ⁶The First Affiliated Hospital, Zhejiang University, zhejiang, China

Introduction: cART-mediated immune reconstitution establishing a tumor-permissive microenvironment. And compromising immune surveillance may contribute to more aggressive disease phenotypes in HIV patients, while few clinical evidence presents. Methods: We conducted a retrospective analysis of clinical data of newly diagnosed HL patients from 2014 to 2024 treated at four medical centers in China. The authors conducted clinical and immune function aspects of HIV positive HL with special emphasis on prognosis and immune factors. Results: 19 patients were diagnosed as HIV positive. HIV positive HL patients had more advance stage, ECOG-PS, bulky disease and B symptoms compared to HL without HIV patients (n=130). HIV positive HL patients had decreased CD4 cell count, CD4/CD8 and less GZMB.Lower CD4 count featured more bulky disease and B symptoms and higher IL-2R and IL-6 level in HIV-HL. And HIV-HL patients with bulky disease have less GZMB compared to non-bulky disease patients. The enrichment impact of gene alterations on bulky disease shown that PI3K/AKT, thyroid hormone signaling, NF-kappa B signaling pathway and EBV infection were involved. While immune dysfunction (CD4, CD8, CD4/CD8) was showed no association with survival in both HIV positive and negative HL. There was similar outcome in patients with and without HIV treated by ABVD chemotherapy.The characteristics of HIV-HL often presented with more aggressive clinical features, while similar outcomes compared with HIV negative HL patients. Impaired immune function may contribute to an increased tumor burden through multiple mechanisms. However, it did not associate with outcomes. HL treatment strategies should not be modified based on HIV status. HL treatment approaches might not necessarily require adjustment solely due to HIV status, but additional clinical evidence is needed to support this assertion in the further.