Validation of the CNS Penetration-Effectiveness Rank for Quantifying Antiretroviral Penetration Into the Central Nervous System
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Open Access
- 1 January 2008
- journal article
- research article
- Published by American Medical Association (AMA) in Archives of Neurology
- Vol. 65 (1) , 65-70
- https://doi.org/10.1001/archneurol.2007.31
Abstract
Over the last 10 years, the use of combination antiretroviral therapy has led to declines in the incidence of complications of human immunodeficiency virus (HIV) infection.1-3 During this same period, the prevalence of neurologic disease has remained stable or increased,4,5 suggesting that treatment of central nervous system (CNS) disease may be suboptimal. One explanation for this may be poor antiretroviral (ARV) penetration into the CNS. Pharmacodynamic models1 and in vivo evidence2 suggest that the tissue-specific concentrations of ARV drugs are important determinants of their effectiveness in that tissue. Whether this is true for specific tissues in humans has been difficult to demonstrate because of technical limitations in sampling and determining tissue drug concentrations and viral loads (VLs). Many investigators have speculated that ARV concentrations in the CNS may be particularly important in treating nervous system disease, but no widely accepted or clinically useful approach to estimating CNS effectiveness exists. This has impeded clinical progress in managing the neurologic complications of HIV.Keywords
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