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

Carina A. Rodriguez, Department of Pediatrics, Division of Infectious Diseases, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Eva Natukunda, Joint Clinical Research Centre, Kampala, Uganda.
Renate Strehlau, VIDA-Nkanyezi Research Unit, Department of Paediatrics and Child Health, University of the Witwatersrand, Johannesburg, South Africa.
Esme L. Venter, The Aurum Institute, Pretoria, South Africa.
Supattra Rungmaitree, Department of Paediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Coleen K. Cunningham, School of Medicine, University of California Irvine (UCI), Irvine, CA, USA; Children's Hospital of Orange County, Orange, CA, USA.
Umesh Lalloo, Durban International Clinical Research Site, Durban University of Technology, Durban, South Africa.
Pope Kosalaraksa, Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Elizabeth HellstrÖm, Be Part Yoluntu Centre, Paarl, South Africa.
Afaaf Liberty, Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa.
Eric J. McGrath, Division of Infectious Diseases & Prevention, Wayne State University School of Medicine, Detroit, MI, USA.
Meenu Kaur, Gilead Sciences, Foster City, CA, USA.
Rory Leisegang, Gilead Sciences, Foster City, CA, USA.
Jason T. Hindman, Gilead Sciences, Foster City, CA, USA.
Vinicius A. Vieira, Gilead Sciences, Foster City, CA, USA.
Kathryn Kersey, Gilead Sciences, Foster City, CA, USA.
Mark F. Cotton, Department of Paediatrics and Child Health, Family Centre for Research with Ubuntu (FAMCRU), Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa.
Natella Rakhmanina, Division of Infectious Diseases, Children's National Hospital, Washington, DC, USA; School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA; Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA.
Aditya H. Gaur, Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA. Electronic address: aditya.gaur@stjude.org.

Document Type

Journal Article

Publication Date

5-1-2024

Journal

The lancet. HIV

Volume

11

Issue

5

DOI

10.1016/S2352-3018(23)00327-2

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 (AUC) and concentration at the end of the dosing interval (C) 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 AUC for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7-119·7); C 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.

Department

Pediatrics

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