This study demonstrated that simian immunodeficiency virus (SIV) infection in rhesus macaques and exposure of microglial cells to HIV-1 Tat protein resulted in the downregulation of miR-124 and increased DNA methylation, suggesting a complex interplay between HIV-1 Tat, miR-124 dysregulation, and epigenetic modifications in the pathogenesis of HAND. This evidence concerns the gene TAT and HIV-associated neurocognitive disorder.