Impact of efavirenz pharmacokinetics and pharmacogenomics on neuropsychological performance in older HIV-infected patients

Uriel Sandkovsky, Anthony T. Podany, Courtney V. Fletcher, Andrew Owen, Angela Felton-Coleman, Lee C. Winchester, Kevin Robertson, Susan Swindells

Research output: Research - peer-reviewArticle

Abstract

Background: Pharmacokinetics (PK) and pharmacodynamics of efavirenz and its 8-hydroxy metabolite (8-OHefavirenz) have not been robustly evaluated in older HIV-infected persons. Objectives: We investigated relationships between neuropsychological (NP) performance and efavirenz and 8-OH-efavirenz PK in HIV-infected individuals > 50 years of age. Methods: A cross-sectional study of HIV-infected adults on an efavirenz-containing regimen. The 12 and 18 h post-dose plasma efavirenz and 8-OH-efavirenz were quantified. CYP2B6 polymorphisms were investigated. Participants underwent neuropsychological tests; surveys were used for depression, sleep quality and anxiety. We investigated potential correlations of efavirenz and 8-OH-efavirenz plasma concentrations with NP performance, sleep, depression, anxiety and CYP2B6 polymorphisms. Results: Thirty participants (24 men and 6 women) with mean age 57 years (range 50-68). Plasma efavirenz concentrations did not correlate with NP performance; however, higher plasma 8-OH-efavirenz correlated with better learning (P=0.002), language (P=0.002) and total NP z-scores (P=0.003). No correlation was seen for efavirenz or 8-OH-efavirenz with sleep, anxiety or depression. Median 12 and 18 h efavirenz plasma concentrations were 1967 ng/mL (IQR 1476-2394) and 1676 ng/mL (IQR 1120-2062), respectively. Median 12 and 18 h 8-OH-efavirenz plasma concentrations were 378 ng/mL (IQR 223-589) and 384 ng/mL (IQR 216-621), respectively. CYP2B6 G516T was associated with significantly higher plasma efavirenz at 12 and 18 h (P=0.02) but not worse NP function. Conclusions: Better neurocognitive functioning was associated with higher 8-OH-efavirenz but not efavirenz plasma concentrations. No correlation was observed with sleep or depression. These findings point to a need for greater understanding of the metabolic profile of efavirenz and 8-OH-efavirenz in plasma and the CNS and relationships with antiviral effect and neurotoxicity.

LanguageEnglish (US)
Pages200-204
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume72
Issue number1
DOIs
StatePublished - 2017

Fingerprint

efavirenz
Pharmacogenetics
Pharmacokinetics
HIV
hydroxide ion
Sleep
Depression
Anxiety
Cytochrome P-450 CYP2B6
Metabolome
Neuropsychological Tests
Antiviral Agents
Language
Cross-Sectional Studies
Learning
Surveys and Questionnaires

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Sandkovsky, U., Podany, A. T., Fletcher, C. V., Owen, A., Felton-Coleman, A., Winchester, L. C., ... Swindells, S. (2017). Impact of efavirenz pharmacokinetics and pharmacogenomics on neuropsychological performance in older HIV-infected patients. Journal of Antimicrobial Chemotherapy, 72(1), 200-204. DOI: 10.1093/jac/dkw403

Impact of efavirenz pharmacokinetics and pharmacogenomics on neuropsychological performance in older HIV-infected patients. / Sandkovsky, Uriel; Podany, Anthony T.; Fletcher, Courtney V.; Owen, Andrew; Felton-Coleman, Angela; Winchester, Lee C.; Robertson, Kevin; Swindells, Susan.

In: Journal of Antimicrobial Chemotherapy, Vol. 72, No. 1, 2017, p. 200-204.

Research output: Research - peer-reviewArticle

Sandkovsky, U, Podany, AT, Fletcher, CV, Owen, A, Felton-Coleman, A, Winchester, LC, Robertson, K & Swindells, S 2017, 'Impact of efavirenz pharmacokinetics and pharmacogenomics on neuropsychological performance in older HIV-infected patients' Journal of Antimicrobial Chemotherapy, vol 72, no. 1, pp. 200-204. DOI: 10.1093/jac/dkw403
Sandkovsky U, Podany AT, Fletcher CV, Owen A, Felton-Coleman A, Winchester LC et al. Impact of efavirenz pharmacokinetics and pharmacogenomics on neuropsychological performance in older HIV-infected patients. Journal of Antimicrobial Chemotherapy. 2017;72(1):200-204. Available from, DOI: 10.1093/jac/dkw403
Sandkovsky, Uriel ; Podany, Anthony T. ; Fletcher, Courtney V. ; Owen, Andrew ; Felton-Coleman, Angela ; Winchester, Lee C. ; Robertson, Kevin ; Swindells, Susan. / Impact of efavirenz pharmacokinetics and pharmacogenomics on neuropsychological performance in older HIV-infected patients. In: Journal of Antimicrobial Chemotherapy. 2017 ; Vol. 72, No. 1. pp. 200-204
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AU - Winchester,Lee C.

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