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Impact of EFV PK/PG on Neuropsychological
Performance in Older HIV+ Patients
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Reported by Jules Levin
CROI 2015 Feb 23-26, Sattle, WA
Uriel Sandkovsky1, Anthony Podany1, Courtney Fletcher1, Angela Felton-Coleman1, Susan Swindells1, Andrew Owen2, Kevin Robertson3
1 University of Nebraska Medical Center, Omaha, Nebraska, United States;2 Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom;3 University of North Carolina, Chapel Hill, North Carolina, United States
This study as you can see in the Summary/conclusion & Results slides just below did not find an association between EFV plasma levels & neurocognitive function but most patients had EFV concentrations in the normal range. But they found better neuro function - total NPZ scores, learning & language function with higher metabolite levels. As it was discussed in the Q&A - there were not very high EFV plasma levels in these pts that is why they did not see a correlation between levels & psych performance; comment by Charles Flexner - none of pts have HCV & having higher metabolite levels might be a surrogate for healthier liver & people with healthier livers tend to perform better on psychiatric performance tests. Based on comments by author in Q&A patients did not have drug abuse either.
In the Q&A David Haas referenced the Thai study oral presentation the day before by Scott Lentendre "showing what looked like a very strong correlation between EFV exposure & neurocognitive performance on standardized psychometric tests in Thailand". The author response, you should listen to on webcast but he said the most import an thing is that they did not see very high plasma concentrations of EFV in these patients & he suggested a few other ideas too....author said - perhaps pts did not have side effects since they were on EFV a long time, so perhaps a self-selection bias to participate in the study, these were very motivated pts.
The discussion in Q&A included that it is hypothesized that older patients might have lower hepatic metabolism but the author said he has not seen.
Scott Letendre Thai study- CROI: Neurocognitive Decline is Associated with Antiretroviral Concentrations in Cerebral Spinal Fluid and Blood - (03/13/15)
webcast: http://www.croiwebcasts.org/console/player/25671?mediaType=slideVideo&
Background: Despite being one of the most commonly prescribed first line antiretroviral agents, the pharmacokinetics (PK) and pharmacodynamics of efavirenz (EFV) and its 8-hydroxy metabolite (8-OH-EFV), have not been robustlyrobustly evaluated in older HIV-infected patients. Moreover, 8-OH-EFV has been shown to be more neurotoxic in vitro than EFV. We sought to investigate relationships between neuropsychological performance (NP) with EFV and 8-OH-EFV PK in HIV-infected individuals >50 yo.
Methods: Cross sectional study of HIV-infected adults >50 yo, on EFV containing ART > 12 weeks. 12 h and 18 h post-dose plasma EFV and 8-OH-EFV were quantified via LC-MS-MS. CYP2B6 polymorphisms were investigated. NP battery assessed executive function, motor skills, verbal learning, memory, and speed of processing, CES-D depression scale and sleep quality index questionnaire were completed. Correlations of EFV and 8-OH-EFV plasma concentrations with NP performance, sleep, depression scores and CYP2B6 polymorphisms were assessed (Spearman's correlation, and univariate logistic regression where appropriate).
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