Limited
drug penetration is an obstacle that is often encountered in the treatment of
CNS diseases including human immunodeficiency virus type-1 (HIV-1)
encephalitis (HIVE). One mechanism that may contribute to this phenomenon is the expression of
ATP-binding cassette (ABC)
drug efflux transporters [i.e.,
P-glycoprotein (P-gp),
Multidrug Resistance-Associated Proteins (MRP/Mrp),
Breast Cancer Resistance
Protein (BCRP; also known as ABCG2)] at the primary brain barrier sites (i.e., blood-brain barrier, blood-cerebrospinal fluid barrier). In addition, it has been recently proposed that glial cells may also contribute to the low accumulation and altered distribution of therapeutic compounds in the CNS by functioning as a "secondary barrier." In fact, a few studies have shown that
ABC transporters are both expressed and functional in glial cells. Furthermore, commonly prescribed antiretroviral compounds (ARVs), particularly
HIV-1 protease inhibitors, are substrates for many of these same
transport proteins suggesting that
ABC transporters in glial cells may contribute to the overall export of these drugs from the brain. HIV-1
infection is a
chronic condition characterized by long-term exposure of brain cellular compartments to HIV-1 virions and soluble
viral proteins. In addition, treatment of HIV-1
infection involves long-term administration of a multiplicity of ARVs (i.e.,
HAART regimens). Indeed, pathological factors associated with HIV-1
infection and/or pharmacological factors related to treatment may alter the expression of
ABC transporters and lead to changes in CNS ARV uptake and/or distribution. This review summarizes recent knowledge in this area and emphasizes the role that glial
ABC transporters may play in regulating ARV transport.