HIV-1 SANCTUARIES AND THE ROLE OF BLOOD-TISSUE BARRIERS: CENTRAL NERVOUS SYSTEM, TESTES, AND RETINA
Tissues that maintain blood-tissue barriers, secondary to microvascular endothelial cell tight junctions, may limit penetration of certain antiretroviral agents and act as partial “drug sanctuaries.” These compartments would potentially include the central nervous system (CNS), the retina, and the testes.1,8,66 A plasma-membrane-localized drug transporter, the P-glycoprotein, was shown to decrease the penetration of protease inhibitors across certain blood-tissue barriers.
As such, substances that block this drug transporter will increase protease inhibitor concentrations across the blood-tissue barriers. This finding may represent a new pharmacologic approach to target relative viral sanctuary sites with higher levels of antiretroviral agents.67 Nevertheless, most analyses show parallel decay of HIV-1 in tissues, compared with peripheral blood, in patients on virally suppressive HAART.51 In addition, free-drug levels, rather than protein-bound drug concentrations, were rarely analyzed in body sites outside the peripheral blood.
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