Using P-gp in Caco-2 cell lines, the NNRTIs nevirapine, efavirenz, and delavirdine were found not to be substrates of this transporter. However, all of these drugs were found to induce the expression and function of P-gp, with nevirapine being the more potent inducer compared with the other two NNRTIs (Stormer et al., 2002). Alternatively, a recent study demonstrated that the effect of P-gp on intracellular HIV-1 replication may be more clinically relevant than the efflux function of P-gp on PIs. The data suggested that high-cellular P-gp activity corresponds with a lower intracellular HIV-1 load in vivo (Sankatsing et al., 2007). Interestingly, Langford et al. (2004) showed that AIDS patients with HIV encephalitis (HIVE) have higher brain P-gp levels than HIVE-negative patients. However, despite studies showing an upregulation of P-gp in HIV-1 infected macrophages, CD4+ T lymphocytes and glial cells (Langford et al., 2004), the pump function of P-gp in HIV-1 infected patients is thought to be decreased (Sankatsing et al., 2004).