Evidence map›Paper›PMID 30168000›Full record

Observational studyEuropean journal of drug metabolism and pharmacokinetics2019

Impact of Efavirenz Metabolism on Loss to Care in Older HIV+ Africans.

Jessie Torgersen, Scarlett L Bellamy, Bakgaki Ratshaa, Xiaoyan Han, Mosepele Mosepele, Athena F Zuppa, Marijana Vujkovic, Andrew P Steenhoff, Gregory P Bisson, Robert Gross

Abstract readObservational Study
In one paragraph

Observational study in European journal of drug metabolism and pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 37% 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. 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

10 authors at 4 institutions in 2 countries.

Jessie TorgersenDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, 3910 Powelton Ave., 2nd Floor, Philadelphia, PA, 19104, USA. jessie.torgersen@uphs.upenn.edu.ORCID http://orcid.org/0000-0002-7861-1421
Scarlett L BellamyDepartment of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, PA, USA.
Bakgaki RatshaaBotswana UPenn Partnership, Gaborone, Botswana.
Xiaoyan HanDepartment of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mosepele MosepeleFaculty of Medicine, University of Botswana, Gaborone, Botswana.
Athena F ZuppaDepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Marijana VujkovicDepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Andrew P SteenhoffBotswana UPenn Partnership, Gaborone, Botswana.
Gregory P BissonDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, 3910 Powelton Ave., 2nd Floor, Philadelphia, PA, 19104, USA.
Robert GrossDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, 3910 Powelton Ave., 2nd Floor, Philadelphia, PA, 19104, USA.
University of Pennsylvania · USChildren's Hospital of Philadelphia · USDrexel University · USUniversity of Botswana · BW

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
Penn Mental Health AIDS Research CenterP30MH097488 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI Karine Dube · 2013 to 2026
$23.5M
Cardiology & pulmonary research training grantT32HL007891 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Jason D Christie · 1998 to 2026
$12.0M
Pharmacogenetics and HIV treatment outcomesR01MH080701 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GROSS, ROBERT · 2009 to 2013
$2.6M
NHLBI NIH HHS T32 HL007891NIAID NIH HHS P30 AI045008NIMH NIH HHS P30 MH097488NIMH NIH HHS R01 MH080701Penn Mental Health AIDS Research Center P30 AI 045008
6 · The paper itself

Abstract

BACKGROUND AND

objectiveEfavirenz is commonly used in Africa and is frequently associated with neurocognitive toxicity, which may compromise clinical outcomes. Older individuals are at increased risk for drug toxicity and clinical outcomes may be worse in older age, particularly among those individuals with cytochrome P450 (CYP) 2B6 polymorphisms associated with slower efavirenz metabolism. The aim of this study was to determine if the CYP2B6 polymorphisms differentially impacts loss to care in older people.

methodsWe conducted a prospective cohort study of 914 treatment-naïve HIV+ adults initiating efavirenz-based antiretroviral treatment at public HIV clinics in Gaborone, Botswana between 2009 and 2013. Older age, defined as age ≥ 50 years, was the primary exposure and loss to care at 6 months was the primary outcome. Interaction between age and CYP2B6 516G>T and 983T>C polymorphisms, defined as extensive, intermediate, and slow metabolism, was assessed. Neurocognitive toxicity was measured using a symptom questionnaire. Age-stratified logistic regression was performed to identify factors associated with loss to care.

resultsOlder age was associated with loss to care (OR 1.95, 95% CI 1.30-2.92). Age modified the effect of CYP2B6 genotype on loss to care with older, slow metabolizers at over four-fold higher risk when compared to older, intermediate metabolizers (OR 4.06 95% CI 1.38-11.89); neurocognitive toxicity did not mediate this risk. CYP2B6 metabolism genotype did not increase risk of loss to care in younger participants.

conclusionOlder age was associated with loss to care, especially among those with slow efavirenz metabolism. Understanding the relationship between older age and CYP2B6 genotype will be important to improving outcomes in an aging population initiating efavirenz-based ART in similar settings.

Indexed as

Black PeopleAdultAge FactorsAlkynesAnti-HIV AgentsBenzoxazinesBotswanaCohort StudiesCyclopropanesCytochrome P-450 CYP2B6FemaleHIV InfectionsHumansMaleMiddle AgedProspective StudiesAlkynesAnti-HIV AgentsBenzoxazinesCyclopropanesCYP2B6 protein, humanCytochrome P-450 CYP2B6efavirenzReverse Transcriptase Inhibitors

Identifiers

PMID30168000
PMCPMC6420397
OpenAlexW2889312730

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.