Using the WHO definition of advanced HIV disease (AHD) (CD4 < 200 cells/mm3 or WHO stage 3/4), recent analyses from sub-Saharan Africa indicate that ~15–30% (or higher) of adults initiating or re-initiating ART present with AHD, with marked heterogeneity by country and population group. The gene discussed is CD4; the disease is mitochondrial DNA depletion syndrome 4a.