HIV-1 protease inhibitors and the MDR1 multidrug transporter.

Hopes for an AIDS cure using triple-combination AIDS therapy have been tempered by problems with partial- or noncompliance with an uncompromisingly rigid drug regimen, the emergence of resistant strains of HIV-1, and pharmacological barriers limiting accessibility of drugs to various critical target tissues and cells. These latter barriers include low bioavailability of the orally administered protease inhibitor (PI) component of the combination therapy, as well as the questionable effectiveness of this treatment strategy for late stage HIV-1 infection with central nervous system (CNS) involvement. Recently, back-to-back reports of hidden reservoirs of fully viable, replication competent, nonmutated HIV-1 viruses in T cells that have survived treatment (1–3) lend credence to the existence of such a barrier. While first pass metabolism by the cytochrome P450 system may partially account for the poor