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

BACKGROUND

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.