Distinct Defects in Marginal Zone B Cells and Filtration Function Characterize Hyposplenism in Persons With HIV-1 on Prolonged ART.

Background: Persons with HIV (PWH) are at increased risk of pneumococcal disease. This study explored filtration and immune function of the spleen, investigating predictors of hyposplenism in PWH on prolonged antiretroviral therapy (ART). Method: We developed a flow cytometry protocol to enumerate Howell-Jolly bodies (HJBs) and marginal zone B cells (MZBs), comparing results from splenectomized patients and healthy donors. We then analyzed HJBs and MZBs in a cross-sectional study to investigate spleen impairment in 96 PWH on prolonged ART. Results: Based on results obtained from asplenic patients and healthy controls, we determined optimal cutoff values of 0.05% for HJBs and 10% for MZBs; these allow accurate differentiation between the 2 groups. HJB results were well correlated with microscopic enumeration of HJBs and pocked red blood cells, considered reference methods for spleen filtration. Among 96 HIV patients on prolonged ART, 9.4% exhibited impaired splenic filtration (HJB >0.05%), associated with a history of AIDS. Older HIV patients showed a higher frequency of HJBs, though only 1 exceeded the pathological threshold. MZBs were significantly decreased in 59.4% of HIV participants, with no correlation between MZB depletion and presence of HJBs. Conclusions: These findings highlight that PWH exhibit depletion of splenic marginal zone B cells, and some demonstrate splenic filtration dysfunction, reflecting persistent splenic impairment despite extended viral suppression. Further research is needed to understand the long-term impact of HIV on splenic function and to develop strategies to improve clinical outcomes in this aging population.