CD4 and infection: Whereas HIV-1 can enter the central nervous system within infected CD4+T-cell and monocytes that traffic across the blood brain barrier, several in vitro and in vivo reports described that free HIV-1 can be taken up by brain endothelial cells in a HS dependant manner, internalized and exocytosed, as a way to cross the blood brain barrier before infection and replication can occur in central nervous system cells such as microglia and astrocytes (61–63).