Evidence map›Paper›PMID 33294914›Full record

ArticleThe Journal of antimicrobial chemotherapy2021

Rifabutin pharmacokinetics and safety among TB/HIV-coinfected children receiving lopinavir/ritonavir-containing second-line ART.

Holly E Rawizza, Regina Oladokun, Emeka Ejeliogu, Stephen Oguche, Babatunde O Ogunbosi, Oche Agbaji, Georgina Odaibo, Godwin Imade, David Olaleye, Lubbe Wiesner and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
0.0field-weighted citation impact, top 57% 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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 2 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. 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

15 authors at 8 institutions in 3 countries.

Holly E RawizzaBrigham and Women's Hospital, Boston, MA, USA.
Regina OladokunCollege of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.
Emeka EjelioguCollege of Health Sciences, Jos University Teaching Hospital, University of Jos, Jos, Nigeria.
Stephen OgucheCollege of Health Sciences, Jos University Teaching Hospital, University of Jos, Jos, Nigeria.
Babatunde O OgunbosiCollege of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.
Oche AgbajiCollege of Health Sciences, Jos University Teaching Hospital, University of Jos, Jos, Nigeria.
Georgina OdaiboCollege of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.
Godwin ImadeCollege of Health Sciences, Jos University Teaching Hospital, University of Jos, Jos, Nigeria.
David OlaleyeCollege of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria.
Lubbe WiesnerDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Kristin M DarinNorthwestern University School of Professional Studies, Chicago, IL, USA.
Prosper OkonkwoAPIN Public Health Initiatives Ltd/Gte, Abuja, Nigeria.
Phyllis J KankiHarvard T.H. Chan School of Public Health, Boston, MA, USA.
Kimberly K ScarsiCollege of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
Helen M McIlleronDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
University of Ibadan · NGUniversity of Jos · NGUniversity of Cape Town · ZAAIDS Prevention Initiative in Nigeria · NGBrigham and Women's Hospital · USHarvard University · USNorthwestern University · USUniversity of Nebraska Medical Center · US

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
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
The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ROBERT A. PARKER · 2004 to 2026
$94.4M
Pharmacokinetic and Programmatic Evaluations to Optimize HIV/TB Co-Treatment Regimens in ChildrenK23AI125122 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI RAWIZZA, HOLLY ELIZABETH · 2016 to 2021
$1.0M
Rifabutin pharmacokinetics and safety among HIV/TB coinfected infants receiving lopinavirR21AI150347 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI RAWIZZA, HOLLY ELIZABETH · 2020 to 2021
$313k
NIAID NIH HHS K23 AI125122NIAID NIH HHS P30 AI060354NIAID NIH HHS R21 AI150347NIAID NIH HHS U01 AI068632NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI106701Wellcome Trust
6 · The paper itself

Abstract

backgroundTreatment options are limited for TB/HIV-coinfected children who require PI-based ART. Rifabutin is the preferred rifamycin for adults on PIs, but the one study evaluating rifabutin with PIs among children was stopped early due to severe neutropenia.

methodsWe evaluated rifabutin safety and plasma pharmacokinetics among coinfected children 3-15 years of age receiving rifabutin 2.5 mg/kg daily with standard doses of lopinavir/ritonavir. The AUC0-24 at 2, 4 and 8 weeks after rifabutin initiation was described using intensive sampling and non-compartmental analysis. Clinical and laboratory toxicities were intensively monitored at 12 visits throughout the study.

resultsAmong 15 children with median (IQR) age 13.1 (10.9-14.0) years and weight 25.5 (22.3-30.5) kg, the median (IQR) rifabutin AUC0-24 was 5.21 (4.38-6.60) μg·h/mL. Four participants had AUC0-24 below 3.8 μg·h/mL (a target for the population average exposure) at week 2 and all had AUC0-24 higher than 3.8 μg·h/mL at the 4 and 8 week visits. Of 506 laboratory evaluations during rifabutin, grade 3 and grade 4 abnormalities occurred in 16 (3%) and 2 (0.4%) instances, respectively, involving 9 (60%) children. Specifically, grade 3 (n = 4) and grade 4 (n = 1) neutropenia resolved without treatment interruption or clinical sequelae in all patients. One child died at week 4 of HIV-related complications.

conclusionsIn children, rifabutin 2.5 mg/kg daily achieved AUC0-24 comparable to adults and favourable HIV and TB treatment outcomes were observed. Severe neutropenia was relatively uncommon and improved with ongoing rifabutin therapy. These data support the use of rifabutin for TB/HIV-coinfected children who require lopinavir/ritonavir.

Indexed as

CoinfectionHIV InfectionsTuberculosisAdolescentAdultChildHumansLopinavirRifabutinRitonavirLopinavirRifabutinRitonavir

Identifiers

PMID33294914
PMCPMC7879135
OpenAlexW3112617262

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Registered trials

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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.