Evidence map›Paper›PMID 41847672›Full record

ArticleIJTLD open2026

Pharmacokinetic modelling as a tool to assess TB treatment adherence: application to the REMEMBER study.

N Abdelgawad, M Chirehwa, H McIlleron, C Kanyama, N Mwelase, A Naidoo, J Kumwenda, M Nyirenda, W P Samaneka, J R Lama and 8 more

Abstract read
In one paragraph

Article in IJTLD open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

18 authors.

N AbdelgawadDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
M ChirehwaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
H McIlleronDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
C KanyamaUniversity of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe, Malawi.
N MwelaseClinical HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa.
A NaidooCenter for the AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal Nelson R. Mandela School of Medicine, Durban, South Africa.
J KumwendaJohns Hopkins Research Project-Kamuzu University of Health Sciences, Blantyre, Malawi.
M NyirendaJohns Hopkins Research Project-Kamuzu University of Health Sciences, Blantyre, Malawi.
W P SamanekaUniversity of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe.
J R LamaAsociación Civil Impacta Salud y Educación, Lima, Peru.
L MohapiPerinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg, South Africa.
V MaveByramjee-Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, India.
V G VelosoFundação Oswaldo Cruz, Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil.
J ValenciaAsociación Civil Impacta Salud y Educación, Lima, Peru.
A GuptaJohn Hopkins University School of Medicine, Baltimore, MD, USA.
M C HosseinipourUniversity of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe, Malawi.
K ScarsiDepartment of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
P DentiDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

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
UZ-UCSF CTUUM1AI069436 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZVAVAHERA MIKE CHIRENJE, LYNDA STRANIX-CHIBANDA · 2012 to 2026
$75.9M
Statistical and Data Management Center for the AIDS Clinical Trials GroupU01AI068634 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HUGHES, MICHAEL DAVID · 2006 to 2010
$71.9M
UZ-UCSF Clinical Trials UnitU01AI069436 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHIRENJE, ZVAVAHERA MIKE · 2007 to 2011
$49.3M
The Malawi Clinical Trials UnitUM1AI069518 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JACKY M JENNINGS, TAHA E TAHA · 2012 to 2026
$43.8M
Soweto Clinical Trials UnitUM1AI069453 · NIAID · WITS HEALTH CONSORTIUM (PTY), LTD · PI Glenda E Gray, Lerato Mohapi · 2012 to 2026
$40.9M
Northwestern University Clinical Trial UnitUM1AI069471 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Chad J Achenbach · 2012 to 2026
$24.6M
NIAID NIH HHS U01 AI068634NIAID NIH HHS U01 AI069436NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069436NIAID NIH HHS UM1 AI069453NIAID NIH HHS UM1 AI069471NIAID NIH HHS UM1 AI069518
6 · The paper itself

Abstract

backgroundThe REMEMBER (A5274) study found that the four-drug TB preventive regimen did not reduce mortality compared to isoniazid-only, raising adherence concerns. Using drug measurements and pharmacometrics, we assessed adherence in the four-drug arm by comparing participants who developed TB (cases) to those who did not (controls).

methodsUsing a 1:4 matched case-control design, we analysed stored blood samples at weeks 2, 4, and 8 since treatment start. Rifampicin and pyrazinamide were measured, and adherence was assessed using two thresholds: i) lower limit of quantification (LLOQ) and ii) personalised thresholds derived from pharmacokinetic simulations. Population pharmacokinetic models and Monte Carlo simulations were used to predict individualised thresholds assuming 100% adherence. Conditional logistic regression compared non-adherence between cases and controls.

resultsAmong 28 cases and 112 controls, the proportion of samples <LLOQ was 52% (cases) versus 45% (controls) for rifampicin and 20% (cases) versus 14% (controls) for pyrazinamide. Non-adherence was significantly higher in cases compared to controls for two pyrazinamide metrics: the week 4 LLOQ (

conclusionPoor adherence may have contributed to TB incidence in REMEMBER. While not definitive, personalised thresholds from model-based simulations remain useful for adherence assessment.

Indexed as

adherencepharmacokinetic modellingpharmacometricsTBITPTtuberculosis

Identifiers

PMID41847672
PMCPMC12991563

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.