Elsevier

Antiviral Research

Volume 82, Issue 2, May 2009, Pages A99-A109
Antiviral Research

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

https://doi.org/10.1016/j.antiviral.2008.12.013Get rights and content
Under a Creative Commons license
open access

Abstract

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.

Abbreviations

BBB
blood–brain barrier
P-gp
P-glycoprotein
MRP
multi-drug resistance associated protein
HAART
highly active antiretroviral therapy
PIs
protease inhibitors
NRTIs
nucleoside reverse transcriptase inhibitors
NNRTIs
non-nucleoside reverse transcriptase inhibitors
NtRTIs
nucleotide reverse transcriptase inhibitors
HAD
HIV-associated dementia
HIVE
HIV encephalitis
MND
mild neurocognitive disorder
MDR-1
multi-drug resistance gene 1
BCRP
breast cancer resistance protein
OAT
organic anion transporter
OATP
organic anion-transporting polypeptide
CSF
cerebrospinal fluid
CNS
central nervous system
AIDS
acquired immunodeficiency syndrome
HAD
HIV-associated dementia
ABC
ATP binding cassette
SLC
solute carrier superfamily
ddI
2′,3′-dideoxyinosine
ddC
2′3′-dideoxycytidine
3TC
(−)-2′-deoxy-3′-thiacytidine
AZT
zidovudine
ENT
equilibrative nucleoside transporter
CNT
concentrative nucleoside transporter
ET-1
endothelin-1
LPS
lipopolysaccharide

Keywords

Blood–brain barrier
Choroid plexus
HIV
HAART
Transporters
P-Glycoprotein
Antiretroviral drugs

Cited by (0)