TRAIL was associated with mononuclear phagocytes (MP) (by colocalisation with HAM‐56) in both the FC and BG regions of HIVE brains.The percentage of macrophages expressing TRAIL in HIVE brain tissue (the ratio of dual HAM‐56‐ and TRAIL‐stained cells to total HAM‐56‐stained cells) was increased (69.4 ± 19% as compared to 52.9 ± 10%, p < 0.01) when compared to PLWH without neurological disease.Additionally, several of the macrophages expressing TRAIL were HIV‐1 infected as detected by co‐localization with HIV‐1 p24 antibodies). This evidence concerns the gene TNFSF10 and nervous system disorder.