Inflammation plays a major role in HAND pathogenesis74–76, and HIV-1 virions, as well as viral proteins such as Tat and gp120, induce the expression and secretion of inflammatory cytokines and chemokines on the human brain endothelium, resulting in endothelial injury and BBB dysfunction, as well as increased infiltration of virions and infected cells into the CNS and neuronal injury77–80. This evidence concerns the gene ITIH4 and HIV-associated neurocognitive disorder.