Evidence map›Paper›PMID 41004270›Full record

Trial reportAntimicrobial agents and chemotherapy2025

Population pharmacokinetics of ritonavir as a booster of lopinavir, atazanavir, or darunavir in African children with HIV.

Lufina Tsirizani, Hylke Waalewijn, Alexander Szubert, Veronica Mulenga, Chishala Chabala, Mutsa Bwakura-Dangarembizi, Moses Chitsamatanga, Diana A Rutebarika, Victor Musiime, Mariam Kasozi and 8 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Observational
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.

Lufina TsirizaniDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0002-4491-4256
Hylke WaalewijnDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Alexander SzubertMedical Research Council Clinical Trials Unit at University College London, London, United Kingdom.ORCID 0000-0002-2082-0861
Veronica MulengaDepartment of Paediatrics and Child Health, University of Zambia, School of Medicine, Lusaka, Zambia.
Chishala ChabalaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Mutsa Bwakura-DangarembiziUniversity of Zimbabwe Clinical Research Centre, Harare, Zimbabwe.
Moses ChitsamatangaUniversity of Zimbabwe Clinical Research Centre, Harare, Zimbabwe.
Diana A RutebarikaDepartment of Paediatrics, joint Clinical Research Centre, Kampala, Uganda.
Victor MusiimeDepartment of Paediatrics, joint Clinical Research Centre, Kampala, Uganda.
Mariam KasoziDepartment of HIV Research, joint Clinical Research Centre, Mbarara, Uganda.
Abbas LugemwaDepartment of HIV Research, joint Clinical Research Centre, Mbarara, Uganda.
Helen M McIlleronDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0002-0982-6226
David M BurgerDepartment of Pharmacy, Radboudumc Research Institute for Medical Innovation (RIMI), Radboud University Medical Center, Nijmegen, the Netherlands.
Diana M GibbMedical Research Council Clinical Trials Unit at University College London, London, United Kingdom.
Angela ColbersDepartment of Pharmacy, Radboudumc Research Institute for Medical Innovation (RIMI), Radboud University Medical Center, Nijmegen, the Netherlands.
Paolo DentiDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0001-7494-079X
Roeland E WasmannDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0002-5769-8150
CHAPAS-4 trial team

Funding

European and Developing Countries Clinical Trials Partnership EDCTP; TRIA2015-1078Gilead Sciences N/AJanssen Pharmaceuticals N/AResearch Council of Norway through the Global Health and Vaccination Programme (GLOBVAC) project number 285284
6 · The paper itself

Abstract

Ritonavir is important in antiretroviral therapy (ART) because it is used to boost the drug exposure of its fellow protease inhibitors (PIs). While PIs are commonly used in children, ritonavir data in this population are quite scarce. We investigated the population pharmacokinetics of ritonavir given to boost exposures of lopinavir, atazanavir, or darunavir, and co-administered with nucleoside reverse transcriptase inhibitors (NRTIs) in African children, and investigated factors affecting its exposure. We conducted a pharmacokinetic sub-study within the CHAPAS-4 (ISRCTN22964075) trial, which randomized children to two NRTIs with twice-daily lopinavir/ritonavir, once-daily atazanavir/ritonavir, or once-daily darunavir/ritonavir, as second-line ART. Intensive pharmacokinetic blood samples were collected at week 6, and nonlinear mixed-effects modeling was used to identify factors affecting ritonavir pharmacokinetics. In all, 170 children were enrolled in the ritonavir-boosted PI arms of the CHAPAS-4 pharmacokinetic sub-study, with median age 10.6 (range 3.2-15.6) years and weight 26.0 (14.2-64.2) kg. Despite similar dose levels, ritonavir exposure varied widely depending on the companion PI. Compared to children on darunavir/ritonavir, those on atazanavir/ritonavir had 137% (95% CI 107%-190%) higher bioavailability and 20% (95% CI 11.3%-31.3%) faster clearance, while those on lopinavir/ritonavir had 23.4% (95% CI 8.20%-34.4%) lower bioavailability. No effect of NRTIs on ritonavir pharmacokinetics was observed. Ritonavir exposure is higher with atazanavir than with lopinavir or darunavir. These data provide greater insight into the use of ritonavir for boosting PIs in children and help reduce the knowledge gap regarding its exposure in children.

Indexed as

Anti-HIV AgentsAtazanavir SulfateDarunavirHIV InfectionsHIV Protease InhibitorsLopinavirRitonavirAdolescentChildChild, PreschoolFemaleHumansMaleAnti-HIV AgentsAtazanavir SulfateDarunavirHIV Protease InhibitorsLopinavirRitonavirNONMEMpediatric antiretroviralpopulation pharmacokineticsprotease inhibitorsritonavir

Identifiers

PMID41004270
PMCPMC12587601

What OpenQuestion holds

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LicenceCC BY
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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.