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Pharmacokinetic Data of Dolutegravir in Second-line Treatment of Children With Human Immunodeficiency Virus: Results From the CHAPAS4 Trial

Bevers, Lisanne AH; Waalewijn, Hylke; Szubert, Alexander J; Chabala, Chishala; Bwakura-Dangarembizi, Mutsa; Makumbi, Shafic; Nangiya, Joan; ... Colbers, Angela; + view all (2023) Pharmacokinetic Data of Dolutegravir in Second-line Treatment of Children With Human Immunodeficiency Virus: Results From the CHAPAS4 Trial. Clinical Infectious Diseases 10.1093/cid/ciad346. (In press). Green open access

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Abstract

BACKGROUND: Dolutegravir (DTG), combined with a backbone of two NRTIs, is currently the preferred first-line treatment for HIV in childhood. CHAPAS4 is an ongoing randomized controlled trial (#ISRCTN22964075) investigating second-line treatment options for children with HIV. We did a nested PK substudy within CHAPAS4 to evaluate the DTG exposure in children with HIV taking DTG with food, as part of their second-line treatment. METHODS: Additional consent was required for children on DTG enrolled in the CHAPAS4-trial to participate in this PK substudy. Children weighing 14-19.9 kg took 25 mg DTG as dispersible tablets (DT) and children ≥20 kg took 50 mg film-coated tablets (FCT). Steady-state 24 h DTG plasma concentration-time PK profiling was done at t = 0 and 1, 2, 4, 6, 8, 12, and 24 h after observed DTG intake with food. Reference adult PK data and paediatric data from the ODYSSEY-trial was used primarily for comparison. The individual target trough concentration (Ctrough) was defined as 0.32 mg/L. RESULTS: 39 children on DTG were included in this PK substudy. The Geometric Mean (GM), (CV%) AUC0-24h was 57.1 h*mg/L (38.4%) which was approximately 8% below the average AUC0-24h in children in the ODYSSEY-trial with comparable dosages, but above the adult reference. The GM (CV%) Ctrough was 0.82 mg/L (63.8%) which was comparable to ODYSSEY and adult reference values. CONCLUSIONS: This nested PK substudy shows that the exposure of DTG taken with food in children on second-line treatment is comparable with that of children in the ODYSSEY-trial and adult references.

Type: Article
Title: Pharmacokinetic Data of Dolutegravir in Second-line Treatment of Children With Human Immunodeficiency Virus: Results From the CHAPAS4 Trial
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/cid/ciad346
Publisher version: https://doi.org/10.1093/cid%2Fciad346
Language: English
Additional information: This is an Open Access article distributed under the terms of the Creative Commons AttributionNonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
Keywords: Science & Technology, Life Sciences & Biomedicine, Immunology, Infectious Diseases, Microbiology, HIV, DTG, pharmacokinetics, children, second-line, SAFETY
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10174031
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