Journal
ANTIVIRAL RESEARCH
Volume 82, Issue 2, Pages A99-A109Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2008.12.013
Keywords
Blood-brain barrier; Choroid plexus; HIV; HAART; Transporters; P-Glycoprotein; Antiretroviral drugs
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Funding
- Wellcome Trust [080268, 057254, 073542] Funding Source: Medline
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The advent of highly active antiretroviral therapy (HAART), which constitutes HIV protease inhibitors. nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors, has dramatically reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) infection in resource-rich countries. However, this disease still kills several million people each year. Though the reason for therapeutic failure is multifactorial, an important concern is the treatment and control of HIV within the central nervous system (CNS). Due to the restricted entry of anti-HIV drugs, the brain is thought to form a viral sanctuary site. This not only results in virological resistance, but also is often associated with the development of complications such as HIV-associated dementia. The CNS delivery of anti-HIV drugs is limited by the blood-brain and blood-CSF interfaces due to a combination of restricted paracellular movement, powerful metabolic enzymes and numerous transporters including members of the ATP binding cassette (ABC) and Solute carrier (SLC) superfalnilies. A better appreciation of the transporters present at the brain barriers will prove a valuable milestone in understanding the limited brain penetration of anti-HIV drugs in HIV and also aid the development of new anti-HIV drugs and drug combinations, with enhanced efficacy in the CNS. This review aims to summarise current knowledge on the transport of anti-HIV drugs across the blood-brain barrier and the choroid plexus, as well as provide recommendations for future research. (C) 2009 Elsevier B.V. All rights reserved.
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