Pathological Proliferation of CD4+ T Cells in Late Presentation of HIV Infection After Antiretroviral Therapy

Hao Liu,1,&ast; Caiping Guo,1,2,&ast; Zhen Li,1,3,&ast; Rui Wang,1,3 Letian Liu,1 Xue Chen,1 Yanmin Liu,4 Yulin Zhang,5 Tong Zhang,1– 3 Yang Zhang1– 3 1Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Beijing Institute of Sexually Transmitted Disease Prevention and Control, Beijing, 100069, People’s Republic of China; 3Beijing Key Laboratory of HIV/AIDS Research, Beijing, 100069, People’s Republic of China; 4Clinical Laboratory Center and Clinical Research Center for Autoimmune Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Zhang; Tong Zhang, Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai, Fengtai District, Beijing, 100069, People’s Republic of China, Email zhangyangdoc@ccmu.edu.cn; zt_doc@ccmu.edu.cnBackground: Despite the global success of antiretroviral therapy (ART) in reducing human immunodeficiency virus (HIV) related morbidity and mortality, late presentation of HIV infection remains a major challenge. This study aims to explore whether the immune dysregulation of pathological proliferation exists in late presenters (LP).Methods: People living with HIV (PLWH) were recruited and divided into LP group (n=55, defined as the presence of an AIDS-defining event and/or CD4 count < 350 cells/μL) and non-late-presenters (n-LP) group (n=54). We evaluated the phenotype and function of CD4+ T cells in PLWH, and their correlation with clinical parameters. Mass cytometry was used to detect and analyze the phenotypic and functional characteristics of CD4+ T cells following ART.Results: The LP exhibited significantly lower CD4+ T cell counts compared to n-LP. A higher proportion of CD4+ T cell subpopulations with characteristics of proliferation (Ki67), activation (HLA-DR), exhaustion (PD-1) and senescence (CD57) was observed in LP. Besides, the proportion of CD4+ T cells with “pathological proliferation” properties (such as Ki67+CD57+, Ki67+HLA-DR+, Ki67+CD38+) in LP was much higher than that in n-LP. We found that the immune dysregulation characterized by pathological proliferation is related to multiple clinical parameters in LP.Conclusion: LP have persistent immune dysfunction post-ART, characterized by excessive and pathological T cell proliferation accompanied by activation or senescence. Future studies focusing on this pathological proliferation phenomenon will be essential to improve immune recovery, long-term prognosis, and health outcomes in advanced patients.Keywords: late presenter, pathological proliferation, human immunodeficiency virus, HIV, immune dysfunction