Waalewijn, H;
Szubert, AJ;
Wasmann, RE;
Wiesner, L;
Chabala, C;
Bwakura-Dangarembizi, M;
Makumbi, S;
Nangiya, J;
Mumbiro, V;
Mulenga, V;
et al.
Waalewijn, H; Szubert, AJ; Wasmann, RE; Wiesner, L; Chabala, C; Bwakura-Dangarembizi, M; Makumbi, S; Nangiya, J; Mumbiro, V; Mulenga, V; Musiime, V; Monkiewicz, LN; Griffiths, AL; Bamford, A; Doerholt, K; Denti, P; Burger, DM; Gibb, DM; McIlleron, HM; Colbers, A; Children with HIV in Africa – Pharmacokinetics and Acceptability
(2023)
First Pharmacokinetic Data of Tenofovir Alafenamide Fumarate and Tenofovir With Dolutegravir or Boosted Protease Inhibitors in African Children: A Substudy of the CHAPAS-4 Trial.
Clin Infect Dis, 77 (6).
pp. 875-882.
ISSN 1537-6591
https://doi.org/10.1093/cid/ciad267
SGUL Authors: Doerholt, Katja
Abstract
BACKGROUND: We evaluated the pharmacokinetics of tenofovir alafenamide fumarate (TAF) and tenofovir in a subset of African children enrolled in the CHAPAS-4 trial. METHODS: Children aged 3-15 years with human immunodeficiency virus infection failing first-line antiretroviral therapy were randomized to emtricitabine/TAF versus standard-of-care nucleoside reverse transcriptase inhibitor combination, plus dolutegravir, atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. Daily emtricitabine/TAF was dosed according to World Health Organization (WHO)-recommended weight bands: 120/15 mg in children weighing 14 to <25 kg and 200/25 mg in those weighing ≥25 kg. At steady state, 8-9 blood samples were taken to construct pharmacokinetic curves. Geometric mean (GM) area under the concentration-time curve (AUC) and the maximum concentration (Cmax) were calculated for TAF and tenofovir and compared to reference exposures in adults. RESULTS: Pharmacokinetic results from 104 children taking TAF were analyzed. GM (coefficient of variation [CV%]) TAF AUClast when combined with dolutegravir (n = 18), darunavir/ritonavir (n = 34), or lopinavir/ritonavir (n = 20) were 284.5 (79), 232.0 (61), and 210.2 (98) ng*hour/mL, respectively, and were comparable to adult reference values. When combined with atazanavir/ritonavir (n = 32), TAF AUClast increased to 511.4 (68) ng*hour/mL. For each combination, tenofovir GM (CV%) AUCtau and Cmax remained below reference values in adults taking 25 mg TAF with a boosted protease inhibitors. CONCLUSIONS: In children, TAF combined with boosted PIs or dolutegravir and dosed according to WHO-recommended weight bands provides TAF and tenofovir concentrations previously demonstrated to be well tolerated and effective in adults. These data provide the first evidence for use of these combinations in African children. CLINICAL TRIALS REGISTRATION: ISRCTN22964075.
Item Type: |
Article
|
Additional Information: |
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: |
HIV, TAF, children, drug interaction, pharmacokinetics, Children with HIV in Africa – Pharmacokinetics and Acceptability of Simple second-line antiretroviral regimens (CHAPAS-4) Trial Team, HIV, TAF, pharmacokinetics, children, drug interaction, 06 Biological Sciences, 11 Medical and Health Sciences, Microbiology |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Clin Infect Dis |
ISSN: |
1537-6591 |
Language: |
eng |
Dates: |
Date | Event |
---|
15 September 2023 | Published | 9 May 2023 | Published Online | 28 April 2023 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
Project ID | Funder | Funder ID |
---|
MC_UU_00004/03 | Medical Research Council | http://dx.doi.org/10.13039/501100000265 | TRIA2015-1078 | European and Developing Countries Clinical Trials Partnership | http://dx.doi.org/10.13039/501100001713 | UM1 AI068634 | South African National Institute of Allergy and Infectious Diseases | UNSPECIFIED | UM1 AI068636 | South African National Institute of Allergy and Infectious Diseases | UNSPECIFIED | UM1 AI106701 | South African National Institute of Allergy and Infectious Diseases | UNSPECIFIED |
|
PubMed ID: |
37315296 |
Web of Science ID: |
WOS:001007114700001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/115544 |
Publisher's version: |
https://doi.org/10.1093/cid/ciad267 |
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