PML-IRIS diagnosis requires a demonstration of HIV replication control on cART—which is a prerequisite to immune recovery—and of an inflammatory response in the infected brain through the detection of gadolinium enhancement and/or edema or mass effect of PML lesions by MRI, and/or parenchymal infiltration of PML lesions by predominantly CD8 T cells and macrophages in brain biopsies (9, 10). This evidence concerns the gene CD8A and progressive multifocal leukoencephalopathy.