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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Pharmacokinetic Data of Dolutegravir in Second-line Treatment of Children With Human Immunodeficiency Virus: Results From the CHAPAS4 Trial
Clinical Infectious Diseases, Volume 77, No. 9, Year 2023
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Description
Background: Dolutegravir (DTG), combined with a backbone of 2 nucleoside reverse transcriptase inhibitors, is currently the preferred first-line treatment for human immunodeficiency virus (HIV) in childhood. CHAPAS4 is an ongoing randomized controlled trial investigating second-line treatment options for children with HIV. We did a nested pharmacokinetic (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 and children ≥20 kg took 50 mg film-coated tablets. Steady-state 24-hour DTG plasma concentration-time PK profiling was done at t = 0 and 1, 2, 4, 6, 8, 12, and 24 hours after observed DTG intake with food. Reference adult PK data and pediatric data from the ODYSSEY trial were used primarily for comparison. The individual target trough concentration (Ctrough) was defined as 0.32 mg/L. Results: Thirty-nine children on DTG were included in this PK substudy. The geometric mean (GM) area under the concentration-time curve over the dosing interval (AUC0-24h) was 57.1 hours × mg/L (coefficient of variation [CV%], 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. Clinical Trials Registration.ISRCTN22964075. © 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Authors & Co-Authors
Waalewijn, Hylke
Netherlands, Nijmegen
Radboud University Medical Center
South Africa, Cape Town
University of Cape Town
Szubert, Alexander J.
United Kingdom, London
Medical Research Council
Chabala, Chishala
Zambia, Lusaka
University Teaching Hospital Lusaka
Bwakura-Dangarembizi, Mutsa F.
Zimbabwe, Harare
University of Zimbabwe
Makumbi, Shafic
Uganda, Mbarara
Mbarara Regional Centre of Excellence
Nangiya, Joan
Uganda, Kampala
Joint Clinical Research Center Uganda
Mumbiro, Vivian
Zimbabwe, Harare
University of Zimbabwe
Mulenga, Veronica
Zambia, Lusaka
University Teaching Hospital Lusaka
Musiime, Victor
Uganda, Kampala
Joint Clinical Research Center Uganda
Burger, David Marinus
Netherlands, Nijmegen
Radboud University Medical Center
Gibb, Diana M.
United Kingdom, London
Medical Research Council
Colbers, Angela P.H.
Netherlands, Nijmegen
Radboud University Medical Center
Statistics
Authors: 12
Affiliations: 7
Identifiers
Doi:
10.1093/cid/ciad346
ISSN:
10584838
Research Areas
Food Security
Infectious Diseases
Maternal And Child Health
Study Approach
Quantitative