CD4 and mitochondrial DNA depletion syndrome 4a: Advanced HIV disease (AHD), defined as a CD4 cell count <200 cells/mm or World Health Organization (WHO) stage 3 or 4 disease, is associated with morbidity and mortality among people living with human immunodeficiency virus (PLHIV), even among those receiving antiretroviral treatment (ART).[1] Individuals with AHD are at high risk for opportunistic infections, such as tuberculosis and cryptococcal meningitis.[2] Management of AHD requires differentiated diagnostics and clinical care beyond routine HIV testing and treatment.[3]