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High efavirenz levels but not neurofilament light plasma levels are associated with poor neurocognitive functioning in asymptomatic HIV patients.
J Neurovirol. 2020 Jun 10 [Online ahead of print]JN

Abstract

The aim of this study is to assess the effect of efavirenz exposure on neurocognitive functioning and investigate plasma neurofilament light (Nfl) as a biomarker for neurocognitive damage. Sub-analysis of the ESCAPE-study, a randomised controlled trial where virologically suppressed, cognitively asymptomatic HIV patients were randomised (2:1) to switch to rilpivirine or continue on efavirenz. At baseline and week 12, patients underwent an extensive neuropsychological assessment (NPA), and serum efavirenz concentration and plasma Nfl levels were measured. Subgroups of elevated (≥ 4.0 mg/L) and therapeutic (0.74 to< 4.0 mg/L) baseline efavirenz concentration were made. Differences between these groups in baseline NPA Z-scores and in delta scores after efavirenz discontinuation were assessed. Nfl level was measured using an ELISA analysis using single molecule array (Simoa) technology. Correlation of plasma NFL with NPA Z-scores was evaluated using a linear mixed model. The elevated group consisted of 6 patients and the therapeutic group of 48. At baseline, the elevated group showed lower composite Z-scores (median - 1.03; IQR 0.87 versus 0.27; 0.79. p 0.02). This effect was also seen on the subdomains verbal (p 0.01), executive functioning (p 0.02), attention (p < 0.01) and speed (p 0.01). In the switch group, the elevated group improved more on composite scores after discontinuing efavirenz (mean 0.58; SD 0.32 versus 0.22; 0.54, p 0.15). No association between plasma Nfl and composite Z-score was found. High efavirenz exposure is associated with worse cognitive functioning compared with patients with therapeutic concentrations. Plasma Nfl is not a suitable biomarker to measure cognitive damage in this group.

Authors+Show Affiliations

Department of Internal Medicine, section Infectious Diseases, University Medical Center (UMC) Utrecht, Utrecht University, PO Box 85500, 3508, GA, Utrecht, the Netherlands. c.s.hakkers@umcutrecht.nl.Department of Internal Medicine, section Infectious Diseases, University Medical Center (UMC) Utrecht, Utrecht University, PO Box 85500, 3508, GA, Utrecht, the Netherlands.Division of Laboratory and Pharmacy, Clinical Pharmacy, University Medical Center (UMC) Utrecht, Utrecht, the Netherlands.Department of Clinical Chemistry, Amsterdam Neuroscience Neurochemistry laboratory, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.Department of Clinical Chemistry, Amsterdam Neuroscience Neurochemistry laboratory, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.Department of Internal Medicine, section Infectious Diseases, University Medical Center (UMC) Utrecht, Utrecht University, PO Box 85500, 3508, GA, Utrecht, the Netherlands.Department of Internal Medicine, section Infectious Diseases, University Medical Center (UMC) Utrecht, Utrecht University, PO Box 85500, 3508, GA, Utrecht, the Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32524424

Citation

Hakkers, Charlotte S., et al. "High Efavirenz Levels but Not Neurofilament Light Plasma Levels Are Associated With Poor Neurocognitive Functioning in Asymptomatic HIV Patients." Journal of Neurovirology, 2020.
Hakkers CS, Hermans AM, van Maarseveen EM, et al. High efavirenz levels but not neurofilament light plasma levels are associated with poor neurocognitive functioning in asymptomatic HIV patients. J Neurovirol. 2020.
Hakkers, C. S., Hermans, A. M., van Maarseveen, E. M., Teunissen, C. E., Verberk, I. M. W., Arends, J. E., & Hoepelman, A. I. M. (2020). High efavirenz levels but not neurofilament light plasma levels are associated with poor neurocognitive functioning in asymptomatic HIV patients. Journal of Neurovirology. https://doi.org/10.1007/s13365-020-00860-1
Hakkers CS, et al. High Efavirenz Levels but Not Neurofilament Light Plasma Levels Are Associated With Poor Neurocognitive Functioning in Asymptomatic HIV Patients. J Neurovirol. 2020 Jun 10; PubMed PMID: 32524424.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High efavirenz levels but not neurofilament light plasma levels are associated with poor neurocognitive functioning in asymptomatic HIV patients. AU - Hakkers,Charlotte S, AU - Hermans,Anne Marie, AU - van Maarseveen,Erik M, AU - Teunissen,Charlotte E, AU - Verberk,Inge M W, AU - Arends,Joop E, AU - Hoepelman,Andy I M, Y1 - 2020/06/10/ PY - 2019/08/27/received PY - 2020/05/19/accepted PY - 2020/05/10/revised PY - 2020/6/12/entrez KW - Asymptomatic KW - Cognition KW - Efavirenz KW - HIV KW - Neurofilament light JF - Journal of neurovirology JO - J. Neurovirol. N2 - The aim of this study is to assess the effect of efavirenz exposure on neurocognitive functioning and investigate plasma neurofilament light (Nfl) as a biomarker for neurocognitive damage. Sub-analysis of the ESCAPE-study, a randomised controlled trial where virologically suppressed, cognitively asymptomatic HIV patients were randomised (2:1) to switch to rilpivirine or continue on efavirenz. At baseline and week 12, patients underwent an extensive neuropsychological assessment (NPA), and serum efavirenz concentration and plasma Nfl levels were measured. Subgroups of elevated (≥ 4.0 mg/L) and therapeutic (0.74 to< 4.0 mg/L) baseline efavirenz concentration were made. Differences between these groups in baseline NPA Z-scores and in delta scores after efavirenz discontinuation were assessed. Nfl level was measured using an ELISA analysis using single molecule array (Simoa) technology. Correlation of plasma NFL with NPA Z-scores was evaluated using a linear mixed model. The elevated group consisted of 6 patients and the therapeutic group of 48. At baseline, the elevated group showed lower composite Z-scores (median - 1.03; IQR 0.87 versus 0.27; 0.79. p 0.02). This effect was also seen on the subdomains verbal (p 0.01), executive functioning (p 0.02), attention (p < 0.01) and speed (p 0.01). In the switch group, the elevated group improved more on composite scores after discontinuing efavirenz (mean 0.58; SD 0.32 versus 0.22; 0.54, p 0.15). No association between plasma Nfl and composite Z-score was found. High efavirenz exposure is associated with worse cognitive functioning compared with patients with therapeutic concentrations. Plasma Nfl is not a suitable biomarker to measure cognitive damage in this group. SN - 1538-2443 UR - https://www.unboundmedicine.com/medline/citation/32524424/High_efavirenz_levels_but_not_neurofilament_light_plasma_levels_are_associated_with_poor_neurocognitive_functioning_in_asymptomatic_HIV_patients L2 - https://dx.doi.org/10.1007/s13365-020-00860-1 DB - PRIME DP - Unbound Medicine ER -
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