The transport of anti-HIV drugs across blood–CNS interfaces: Summary of current knowledge and recommendations for further research

• Published in: Antiviral research Vol. 82; no. 2; pp. A99 - A109
• Main Authors: Varatharajan, Lavanya, Thomas, Sarah A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2009; Elsevier
• Subjects: Animals; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Biological Transport; Blood-Brain Barrier - drug effects; Blood-Nerve Barrier - drug effects; Blood–brain barrier; Choroid plexus; HAART; HIV; HIV Infections - drug therapy; HIV Infections - metabolism; Human immunodeficiency virus; Humans; Membrane Transport Proteins - metabolism; P-Glycoprotein; Review; Transporters; Choroid plexus; MND; ABC; ddC; BBB; OAT; NNRTIs; ddI; CNT; CNS; MRP; ENT; SLC; LPS; Blood–brain barrier; NtRTIs; HIVE; CSF; Transporters; PIs; P-Glycoprotein; BCRP; Antiretroviral drugs; MDR-1; 3TC; P-gp; AIDS; HAD; OATP; NRTIs; ET-1; HIV; AZT; HAART
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2008.12.013

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 multi-factorial, 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) superfamilies. 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.