Penetration and Effectiveness of Antiretroviral Therapy in the Central Nervous System

ISSN: 1875-614X (Online)
ISSN: 1871-5230 (Print)


Volume 15, 3 Issues, 2016


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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents

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Editor-in-Chief:
Claudiu T. Supuran
Neurofarba Department
University of Florence
Florence
Italy


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Penetration and Effectiveness of Antiretroviral Therapy in the Central Nervous System



Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 8(2): 169-183.

Author(s): Scott Letendre, Ronald J. Ellis, Brookie Best, Archana Bhatt, Jennifer Marquie-Beck, Shannon LeBlanc, Steven Rossi, Edmund Capparelli and J Allen McCutchan.

Affiliation: University of California, San Diego, HIV Neurobehavioral Research Center, 150 W. Washington St, First Floor, San Diego, California 92103 USA.

Abstract

Combination antiretroviral therapy (ART) has markedly reduced morbidity and mortality among HIV-infected individuals but not the prevalence of HIV-associated neurocognitive disorders (HAND). Several conditions may be responsible for the high prevalence of cognitive impairment, including incomplete suppression of HIV in nervous system by some antiretrovirals. Since individuals with HAND have a lower quality of life, worse medication adherence, and a higher risk of death, optimizing treatment of neurocognitive outcomes is an important goal of therapy. Optimization of ART to treat the CNS is limited, in part, by the ability of many antiretrovirals to cross the blood-brain barrier (BBB). Differences between antiretrovirals in crossing the BBB – and by extension differences in their concentrations in the brain – may explain inter-individual differences in susceptibility to HAND among treated individuals. This manuscript reviews relevant data on the CSF pharmacology of antiretrovirals and accumulating evidence that the use of drugs that reach therapeutic concentrations in the CNS are the best options to prevent and treat HIV-induced brain injury. Despite the importance of healthy cognition to the quality of patients lives, consensus treatment guidelines for HAND have yet to be formulated more than two decades after its first description. Formulating widely accepted recommendations for CNS-optimized treatment strategies requires a level of clinical evidence not yet developed but studies are underway to address this shortcoming.

Keywords:

HIV, Antiretrovirals, Pharmacology, Cerebrospinal Fluid.



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Article Details

Volume: 8
Issue Number: 2
First Page: 169
Last Page: 183
Page Count: 15
DOI: 10.2174/187152309789152057
Price: $58
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