title: Role and modulation of drug transporters in HIV-1 therapy.
abstract: Current treatment of human immunodeficiency virus type-1 (HIV-1) infection involves a combination of antiretroviral drugs (ARVs) that target different stages of the HIV-1 life cycle. This strategy is commonly referred to as highly active antiretroviral therapy (HAART) or combined antiretroviral therapy (cART). Membrane-associated drug transporters expressed ubiquitously in mammalian systems play a crucial role in modulating ARV disposition during HIV-1 infection. Members of the ATP-binding cassette (ABC) and solute carrier (SLC) transporter superfamilies have been shown to interact with ARVs, including those that are used as part of first-line treatment regimens. As a result, the functional expression of drug transporters can influence the distribution of ARVs at specific sites of infection. In addition, pathological factors related to HIV-1 infection and/or ARV therapy itself can alter transporter expression and activity, thus further contributing to changes in ARV disposition and the effectiveness of HAART. This review summarizes current knowledge on the role of drug transporters in regulating ARV transport in the context of HIV-1 infection.
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 2S2, Canada.
authors.forename: Camille
authors.initials: C
authors.lastname: Alam
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 2S2, Canada.
authors.forename: Sana-Kay
authors.initials: SK
authors.lastname: Whyte-Allman
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 2S2, Canada.
authors.forename: Amila
authors.initials: A
authors.lastname: Omeragic
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 2S2, Canada. Electronic address: r.bendayan@utoronto.ca.
authors.forename: Reina
authors.initials: R
authors.lastname: Bendayan
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active; D001693:Biological Transport, Active; D004337:Drug Carriers; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans
chemical_list: D019380:Anti-HIV Agents; D004337:Drug Carriers
keywords: ABC transporter; Antiretroviral drugs; Blood–tissue barriers; Drug disposition; HIV-1; Nuclear receptors; SLC transporter