Evidence map›Paper›PMID 27655857›Full record

ArticleThe Journal of antimicrobial chemotherapy2017

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

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05678660 (Study of Neurological Aging Among People Living With HIV), which is not on this map. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05678660 active not recruitingnot on this mapstarted 2022, after this paper: background citation

Study of Neurological Aging Among People Living With HIV (SNAP)

TypeobservationalSponsorUniversity of RochesterRan2022 to 2027Enrolled298ConditionsAging, Premature
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Neurocognitive Impairment and Associated Genetic Aspects in HIV Infection.Current topics in behavioral neurosciences · 2021
    Article
  6. Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Uriel SandkovskyDivision of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, USA usandkovsky@unmc.edu.
Anthony T PodanyDepartment of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
Courtney V FletcherDivision of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Andrew OwenMolecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Angela Felton-ColemanDivision of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Lee C WinchesterDepartment of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
Kevin RobertsonDepartment of Neurology, University of North Carolina, Chapel Hill, NC, USA.
Susan SwindellsDivision of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Nebraska Medical Center · USUniversity of Nebraska Medical Center · USUniversity of Liverpool · GBUniversity of North Carolina at Chapel Hill · US

Funding

Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
Therapeutics Core (Page 286)P30MH062261 · NIMH · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI GENDELMAN, HOWARD E · 2000 to 2021
$37.7M
NIAID NIH HHS UM1 AI106701NIMH NIH HHS P30 MH062261
6 · The paper itself

Abstract

backgroundPharmacokinetics (PK) and pharmacodynamics of efavirenz and its 8-hydroxy metabolite (8-OH-efavirenz) have not been robustly evaluated in older HIV-infected persons.

objectivesWe investigated relationships between neuropsychological (NP) performance and efavirenz and 8-OH-efavirenz PK in HIV-infected individuals >50 years of age.

methodsA 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.

resultsThirty 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.

conclusionsBetter 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.

Indexed as

AgedAIDS Dementia ComplexAlkynesAnxietyBenzoxazinesCross-Sectional StudiesCyclopropanesCytochrome P-450 CYP2B6DepressionFemaleHIV InfectionsHumansMaleMiddle AgedNeuropsychological TestsPharmacogeneticsAlkynesBenzoxazinesCyclopropanesCytochrome P-450 CYP2B6efavirenzReverse Transcriptase Inhibitors

Identifiers

PMID27655857
PMCPMC5161051
OpenAlexW2523248656

What OpenQuestion holds

Textmetadata
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.