To support the 2025 revision of the WHO guidelines for managing AHD, we updated and expanded the 2014 systematic review[14] to investigate the diagnostic accuracy of the WHO clinical staging system for identification of individuals with AHD as defined by a CD4 cell count of <200 cells/μL in PLHIV at any point of their individual history. Here, CD4 is linked to mitochondrial DNA depletion syndrome 4a.