HIV-Tat, a protein thought to be responsible for the vascular abnormalities and neurotoxicity in HIV, also induces the expression of P-gp in brain endothelial cells which correlated with a functional upregulation of the transporter function of P-gp (Hayashi et al., 2005). A similar change in P-gp expression has been observed following chronic exposure of bovine brain microvessel endothelial cells to ritonavir. In fact, the HIV PI increased P-gp activity and expression in a concentration-dependent manner in this in vitro model of the BBB, raising the possibility that HAART could itself contribute to the brain as a HIV sanctuary site by the induction of drug transporters (Perloff et al., 2007). Collectively, these studies suggest that the selective inhibition of P-gp may facilitate the entry of PIs and certain NRTIs into viral sanctuaries and enhance the concentration of anti-HIV drugs in these sites to therapeutic levels.