Evidence map›Paper›PMID 27116047›Full record

ArticleJournal of acquired immune deficiency syndromes (1999)2016

Plasma Efavirenz Exposure, Sex, and Age Predict Virological Response in HIV-Infected African Children.

Andrzej Bienczak, Paolo Denti, Adrian Cook, Lubbe Wiesner, Veronica Mulenga, Cissy Kityo, Addy Kekitiinwa, Diana M Gibb, David Burger, A Sarah Walker and 1 more

Abstract read
In one paragraph

Article in Journal of acquired immune deficiency syndromes (1999), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

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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

11 authors.

Andrzej Bienczak*Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa; †MRC Clinical Trials Unit, University College London, London, United Kingdom; ‡Department of Paediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia; §Joint Clinical Research Centre, Kampala, Uganda; ‖Baylor College of Medicine Bristol Myers Squibb Children's Clinical Centre of Excellence, Kampala, Uganda/Gulu Regional Centre of Excellence, Gulu, Uganda; and ¶Department of Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
Paolo Denti
Adrian Cook
Lubbe Wiesner
Veronica Mulenga
Cissy Kityo
Addy Kekitiinwa
Diana M Gibb
David Burger
A Sarah Walker
Helen McIlleron

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
LOC-IMPAACT Leadership GroupPharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant Women in the USUM1AI068632 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI Sharon A Nachman · 2011 to 2026
$278.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
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
International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) GroupU01AI068632 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI JACKSON, J BROOKS · 2006 to 2010
$109.7M
Medical Research Council MC_UU_12023/26NIAID NIH HHS U01 AI068632NIAID NIH HHS UM1 AI068632NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI106701
6 · The paper itself

Abstract

backgroundOwing to insufficient evidence in children, target plasma concentrations of efavirenz are based on studies in adults. Our analysis aimed to evaluate the pediatric therapeutic thresholds and characterize the determinants of virological suppression in African children.

methodsWe analyzed data from 128 African children (aged 1.7-13.5 years) treated with efavirenz, lamivudine, and one among abacavir, stavudine, or zidovudine, and followed up to 36 months. Individual pharmacokinetic (PK) measures [plasma concentration 12 hours after dose (C12h), plasma concentration 24 hours after dose (C24h), and area under the curve (AUC0-24)] were estimated using population PK modeling. Cox multiple failure regression and multivariable fractional polynomials were used to investigate the risks of unsuppressed viral load associated with efavirenz exposure and other factors among 106 initially treatment-naive children, and likelihood profiling was used to identify the most predictive PK thresholds.

resultsThe risk of viral load >100 copies per milliliter decreased by 42% for every 2-fold increase in efavirenz mid-dose concentration [95% confidence interval (CI): 23% to 57%; P < 0.001]. The most predictive PK thresholds for increased risk of unsuppressed viral load were C12h 1.12 mg/L [hazard ratio (HR): 6.14; 95% CI: 2.64 to 14.27], C24h 0.65 mg/L (HR: 6.57; 95% CI: 2.86 to 15.10), and AUC0-24 28 mg·h/L (HR: 5.77; 95% CI: 2.28 to 14.58). Children older than 8 years had a more than 10-fold increased risk of virological nonsuppression (P = 0.005); among children younger than 8 years, boys had a 5.31 times higher risk than girls (P = 0.007). Central nervous system adverse events were infrequently reported.

conclusionsOur analysis suggests that the minimum target C24h and AUC0-24 could be lowered in children. Our findings should be confirmed in a prospective pediatric trial.

Indexed as

AdolescentAge FactorsAlkynesBenzoxazinesChildCyclopropanesFemaleHIV InfectionsHumansMaleMultivariate AnalysisReverse Transcriptase InhibitorsSex FactorsAlkynesBenzoxazinesCyclopropanesefavirenzReverse Transcriptase Inhibitors

Identifiers

PMID27116047
PMCPMC5172513

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.