Evidence map›Paper›PMID 29855606›Full record

ArticleThe pharmacogenomics journal2018

Polymorphisms in cytochrome P450 are associated with extensive efavirenz pharmacokinetics and CNS toxicities in an HIV cohort in Botswana.

Marijana Vujkovic, Scarlett L Bellamy, Athena F Zuppa, Marc R Gastonguay, Ganesh S Moorthy, Bakgaki Ratshaa, Xiaoyan Han, Andrew P Steenhoff, Mosepele Mosepele, Brian L Strom and 3 more

Open access · greenAbstract read
In one paragraph

Article in The pharmacogenomics journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 25% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Approaches to repurposing reverse transcriptase antivirals in cancer.British journal of clinical pharmacology · 2025
    Review
  5. Review
  6. Integrase Inhibitors are Associated with Neuropsychiatric Symptoms in Women with HIV.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023
    Article
  7. Review
  8. Article
  9. Genetic Variants in Smoking-Related Genes in Two Smoking Cessation Programs: A Cross-Sectional Study.International journal of environmental research and public health · 2021
    Article
  10. Association ofPharmacogenomics and personalized medicine · 2021
    Article
  11. 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

13 authors at 6 institutions in 2 countries.

Marijana VujkovicCenter for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4924-5714
Scarlett L BellamyDepartment of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA.
Athena F ZuppaDepartment of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Marc R GastonguayMetrum Research Group, Tariffville, CT, USA.
Ganesh S MoorthyDepartment of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Bakgaki RatshaaBotswana UPenn Partnership, Gaborone, Botswana.
Xiaoyan HanCenter for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Andrew P SteenhoffDepartment of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Mosepele MosepeleFaculty of Medicine, University of Botswana, Gaborone, Botswana.
Brian L StromRutgers Biomedical and Health Sciences, Newark, NJ, USA.
Gregory P BissonCenter for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Richard AplencDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Robert GrossCenter for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. grossr@upenn.edu.
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · USDrexel University · USMetrum Research Group (United States) · USRutgers, The State University of New Jersey · USUniversity of Botswana · BW

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6M
Penn Mental Health AIDS Research CenterP30MH097488 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI Knashawn Hodge Morales · 2013 to 2026
$23.5M
Pharmacogenetics and HIV treatment outcomesR01MH080701 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GROSS, ROBERT · 2009 to 2013
$2.6M
NIAID NIH HHS P30 AI045008NIMH NIH HHS P30 MH097488NIMH NIH HHS R01 MH080701
6 · The paper itself

Abstract

Inter-individual variability in efavirenz (EFV) pharmacokinetics and dynamics is dominantly driven by the polymorphism in cytochrome P450 (CYP) isoenzyme 2B6 516G>T. We hypothesized that additional CYP polymorphisms mediate the relationship between CYP2B6 516G>T, EFV metabolism, and clinical events. We investigated 21 SNPs in 814 HIV-infected adults initiating EFV-based therapy in Botswana for population pharmacokinetics, CNS toxicities, and treatment outcomes. Two SNPs (rs28399499 and rs28399433) showed reduced apparent oral EFV clearance. Four SNPs (rs2279345, rs4803417, rs4802101, and rs61663607) showed extensive clearance. Composite CYP2B-mediated EFV metabolism was significantly associated with CNS toxicity (p = 0.04), with extensive metabolizers reporting more and slow and very slow metabolizers reporting less toxicity after 1 month compared to intermediate metabolizers. Composite CYP2B6 metabolism was not associated with composite early treatment failure. In conclusion, our data suggest that CNS-related toxicities might not be solely the result of super-therapeutic parent EFV concentrations in HIV-infected individuals in patients of African ancestry.

Indexed as

AdultAlkynesAllelesBenzoxazinesBotswanaCentral Nervous SystemCohort StudiesCyclopropanesCytochrome P-450 Enzyme SystemFemaleGenotypeHIV InfectionsHumansMalePolymorphism, Single NucleotideReverse Transcriptase InhibitorsAlkynesBenzoxazinesCyclopropanesCytochrome P-450 Enzyme SystemefavirenzReverse Transcriptase Inhibitors

Identifiers

PMID29855606
PMCPMC6151142
OpenAlexW2805340383

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.