Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system

Scott Letendre, Jennifer Marquie-Beck, Edmund Capparelli, Brookie Best, David Clifford, Ann C. Collier, Benjamin Gelman, Justin C. McArthur, J. Allen McCutchan, Susan Morgello, David Simpson, Igor Grant, Ronald J. Ellis

Research output: Contribution to journalArticle

555 Citations (Scopus)

Abstract

Objective: To evaluate whether penetration of a combination regimen into the central nervous system (CNS), as estimated by the CNS Penetration- Effectiveness (CPE) rank, is associated with lower cerebrospinal fluid (CSF) viral load. Design: Data were analyzed from 467 participants who were human immunodeficiency virus (HIV) seropositive and who reported antiretroviral (ARV) drug use. Individual ARV drugs were assigned a penetration rank of 0 (low), 0.5 (intermediate), or 1 (high) based on their chemical properties, concentrations in CSF, and/or effectiveness in the CNS in clinical studies. The CPE rank was calculated by summing the individual penetration ranks for each ARV in the regimen. Results: The median CPE rank was 1.5 (interquartile range, 1-2). Lower CPE ranks correlated with higher CSF viral loads. Ranks less than 2 were associated with an 88% increase in the odds of detectable CSF viral load. In multivariate regression, lower CPE ranks were associated with detectable CSF viral loads even after adjusting for total number of ARV drugs, ARV drug adherence, plasma viral load, duration and type of the current regimen, and CD4 count. Conclusions: Poorer penetration of ARV drugs into the CNS appears to allow continued HIV replication in the CNS as indicated by higher CSF HIV viral loads. Because inhibition of HIV replication in the CNS is probably critical in treating patients who have HIV-associated neurocognitive disorders, ARV treatment strategies that account for CNS penetration should be considered in consensus treatment guidelines and validated in clinical studies.

Original languageEnglish (US)
Pages (from-to)65-70
Number of pages6
JournalArchives of Neurology
Volume65
Issue number1
DOIs
StatePublished - Jan 2008

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Viral Load
Cerebrospinal Fluid
Central Nervous System
HIV
Virus Replication
Pharmaceutical Preparations
Central Nervous System Agents
CD4 Lymphocyte Count
Penetration
Consensus
Guidelines
Therapeutics
Drugs
AIDS/HIV

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Letendre, S., Marquie-Beck, J., Capparelli, E., Best, B., Clifford, D., Collier, A. C., ... Ellis, R. J. (2008). Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Archives of Neurology, 65(1), 65-70. https://doi.org/10.1001/archneurol.2007.31

Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. / Letendre, Scott; Marquie-Beck, Jennifer; Capparelli, Edmund; Best, Brookie; Clifford, David; Collier, Ann C.; Gelman, Benjamin; McArthur, Justin C.; McCutchan, J. Allen; Morgello, Susan; Simpson, David; Grant, Igor; Ellis, Ronald J.

In: Archives of Neurology, Vol. 65, No. 1, 01.2008, p. 65-70.

Research output: Contribution to journalArticle

Letendre, S, Marquie-Beck, J, Capparelli, E, Best, B, Clifford, D, Collier, AC, Gelman, B, McArthur, JC, McCutchan, JA, Morgello, S, Simpson, D, Grant, I & Ellis, RJ 2008, 'Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system', Archives of Neurology, vol. 65, no. 1, pp. 65-70. https://doi.org/10.1001/archneurol.2007.31
Letendre, Scott ; Marquie-Beck, Jennifer ; Capparelli, Edmund ; Best, Brookie ; Clifford, David ; Collier, Ann C. ; Gelman, Benjamin ; McArthur, Justin C. ; McCutchan, J. Allen ; Morgello, Susan ; Simpson, David ; Grant, Igor ; Ellis, Ronald J. / Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. In: Archives of Neurology. 2008 ; Vol. 65, No. 1. pp. 65-70.
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