Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study
Issued Date
2024-05-01
Resource Type
eISSN
23523018
Scopus ID
2-s2.0-85191556215
Pubmed ID
38621393
Journal Title
The Lancet HIV
Volume
11
Issue
5
Start Page
e300
End Page
e308
Rights Holder(s)
SCOPUS
Bibliographic Citation
The Lancet HIV Vol.11 No.5 (2024) , e300-e308
Suggested Citation
Rodriguez C.A., Natukunda E., Strehlau R., Venter E.L., Rungmaitree S., Cunningham C.K., Lalloo U., Kosalaraksa P., HellstrÖm E., Liberty A., McGrath E.J., Kaur M., Leisegang R., Hindman J.T., Vieira V.A., Kersey K., Cotton M.F., Rakhmanina N., Gaur A.H. Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study. The Lancet HIV Vol.11 No.5 (2024) , e300-e308. e308. doi:10.1016/S2352-3018(23)00327-2 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98228
Title
Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study
Author's Affiliation
Siriraj Hospital
Elizabeth Glaser Pediatric AIDS Foundation
Joint Clinical Research Center Uganda
Chris Hani Baragwanath Hospital
Faculty of Medicine, Khon Kaen University
The George Washington University School of Medicine and Health Sciences
St. Jude Children's Research Hospital
Wayne State University School of Medicine
The Aurum Institute
University of the Witwatersrand, Johannesburg
Morsani College of Medicine
Tygerberg Hospital
UCI School of Medicine
CHOC Children‘s UC Irvine School of Medicine
Childrens National Health System
Durban University of Technology
Gilead Sciences Incorporated
Be Part Yoluntu Centre
Elizabeth Glaser Pediatric AIDS Foundation
Joint Clinical Research Center Uganda
Chris Hani Baragwanath Hospital
Faculty of Medicine, Khon Kaen University
The George Washington University School of Medicine and Health Sciences
St. Jude Children's Research Hospital
Wayne State University School of Medicine
The Aurum Institute
University of the Witwatersrand, Johannesburg
Morsani College of Medicine
Tygerberg Hospital
UCI School of Medicine
CHOC Children‘s UC Irvine School of Medicine
Childrens National Health System
Durban University of Technology
Gilead Sciences Incorporated
Be Part Yoluntu Centre
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg. Methods: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with ClinicalTrials.gov, NCT02881320. Findings: Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUCtau for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7–119·7); Ctau was 34·6% lower than adults (65·4%, 49·1–87·2). Both parameters were within the target exposure range previously found in adults, children, or both”. Grade 3–4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3–4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48. Interpretation: Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg. Funding: Gilead Sciences.