Evidence map›Paper›PMID 35377434›Full record

Observational studyClinical infectious diseases : an official publication of the Infectious Diseases Society of America2022

Pharmacokinetics and Safety of Bedaquiline in Human Immunodeficiency Virus (HIV)-Positive and Negative Older Children and Adolescents With Rifampicin-Resistant Tuberculosis.

Jennifer A Hughes, Belén P Solans, Heather R Draper, H Simon Schaaf, Jana L Winckler, Louvina van der Laan, Kendra K Radtke, Barend Fourie, Lubbe Wiesner, Anneke C Hesseling and 2 more

Open access · bronzeAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the 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
1.3field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Population pharmacokinetics of bedaquiline: a systematic review.European journal of clinical pharmacology · 2025
    Pooled it
  3. Article
  4. Review
  5. Observational
  6. Article
  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

12 authors at 5 institutions in 2 countries.

Jennifer A HughesDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-5349-9509
Belén P SolansDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine, San Francisco, California, USA.
Heather R DraperDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
H Simon SchaafDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Jana L WincklerDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Louvina van der LaanDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Kendra K RadtkeDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine, San Francisco, California, USA.
Barend FourieDepartment of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Lubbe WiesnerDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0002-9070-8699
Anneke C HesselingDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Radojka M SavicDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine, San Francisco, California, USA.
Anthony J Garcia-PratsDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Desmond Tutu HIV Foundation · ZAUniversity of California, San Francisco · USUniversity of Cape Town · ZAUniversity of Wisconsin–Madison · USWestern Cape Department of Health · ZA

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 Jennifer Jao, 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
LC - IMPAACT Leadership GroupUM1AI106716 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$47.2M
Optimizing and operationalizing pediatric drug-resistant tuberculosis treatmentR01HD083047 · NICHD · STELLENBOSCH UNIVERSITY · PI GARCIA-PRATS, ANTHONY JOSEPH, SAVIC, RADOJKA · 2015 to 2019
$1.6M
NIAID NIH HHS U01 AI068632NIAID NIH HHS UM1 AI068632NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI106701NIAID NIH HHS UM1 AI106716NICHD NIH HHS R01 HD083047NIH HHS R01HD083047
6 · The paper itself

Abstract

backgroundPharmacokinetic data for bedaquiline in children are limited. We described the pharmacokinetics and safety of bedaquiline in South African children and adolescents receiving treatment for multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) in routine care.

methodsIn this observational cohort study, children aged 6-17 years receiving bedaquiline at recommended doses as part of MDR/RR-TB treatment underwent semi-intensive pharmacokinetic sampling. Bedaquiline and the M2 metabolite plasma concentrations were quantified, and nonlinear mixed-effects modeling performed. Pediatric data were described using a pre-established model of bedaquiline pharmacokinetics in adults. The exposure reference was 187 µg ⋅ h/mL, the median weekly area under the curve (AUC) of adults at week 24 of treatment with bedaquiline. Safety was assessed through monthly clinical, blood and electrocardiogram monitoring, and treatment outcomes described.

resultsFifteen children (3 human immunodeficiency virus [HIV]-positive) with median age 13.3 years (range 6.5-16.3) were included. A bedaquiline pharmacokinetic model was adapted to be allometrically scaled in clearance and volume, centered in the median child population weight. Bedaquiline bioavailability was 57% of that in adults. Overall bedaquiline exposures were below target, and AUC reference attainment was achieved in only 3 (20%) children. Ten children experienced 27 adverse events at least possibly related to bedaquiline; no adverse events led to bedaquiline withdrawal. Two adverse events (arthritis and arthralgia) were considered severe, and 2 children had mild QT interval corrected for heart rate using Fridericia's formula (QT) prolongation.

conclusionsThe evaluated doses of bedaquiline in children ≥ 6 years of age were safe but achieved slightly lower plasma concentrations compared to adults receiving the recommended dose, possibly due to delayed food intake relative to bedaquiline administration.

Indexed as

HIV InfectionsHIV SeropositivityTuberculosis, Multidrug-ResistantAdolescentAdultAntitubercular AgentsChildDiarylquinolinesHIVHumansRifampinAntitubercular AgentsbedaquilineDiarylquinolinesRifampinbedaquilinechildrenpharmacokineticsRR-TBsafety

Identifiers

PMID35377434
PMCPMC9662178
OpenAlexW4225818186

What OpenQuestion holds

Textmetadata
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.