The diagnosis of IRIS should thus be suspected whenever the clinical features of PML worsen, or start 4–8 weeks after the initiation of HAART, and the CD4+ count is less than 100 cells/mm3 before the initiation of HAART [60], or when neurological symptoms develop or worsen while on HAART. This evidence concerns the gene CD4 and progressive multifocal leukoencephalopathy.