Research in context
Evidence before this study
Integrase strand-transfer inhibitors (INSTIs) are the preferred third agents within a complete antiviral regimen for treatment of HIV in children globally. Coformulated emtricitabine and tenofovir alafenamide is a preferred component in antiretroviral regimens for children in the USA and the European Union. Data in adult populations support the use of fixed-dose combinations for the treatment of HIV; single-tablet regimens are recommended for enhancement of adherence and are also considered optimum for children. Many fixed-dose combinations recommended for adults are also recommended for adolescents, but not for children (especially those with bodyweight <25 kg) due to weight restrictions. Approval for these fixed-dose combinations have mainly been based on data derived from use of the individual components in participants included in paediatric studies rather than from the fixed-dose product itself. We searched PubMed for articles published between Jan 1, 1997, and Sept 30, 2020, using each of the search terms “tenofovir alafenamide” or “bictegravir”, “children”, “adolescent” or “pediatric”, “trial” or “study”, limited to English language articles. The search yielded two articles on the safety, efficacy, and pharmacokinetics of the single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide: one study in 50 treatment-naive adolescents with HIV (aged 12 to <18 years) at week 48 and another study in 23 virologically suppressed children (aged 6 to <12 years) at week 24. Results of these studies showed that this single-tablet regimen was safe, well tolerated, and maintained high rates of virological efficacy in children and adolescents. Our search identified no articles of the fixed-dose combination containing bictegravir, emtricitabine, and tenofovir alafenamide in children and adolescents.
Added value of this study
This is the first report of pharmacokinetic, safety, and efficacy data for the single-tablet regimen containing bictegravir coformulated with emtricitabine and tenofovir alafenamide, given once daily for 48 weeks in paediatric participants (aged 6 to <18 years) with a bodyweight of at least 25 kg. In our study, population pharmacokinetic modelling showed that the area under the curve at the end of the dosing interval (AUCtau) and maximum plasma concentration (Cmax) of bictegravir in adolescents were similar to that in adults, and bictegravir concentrations at the end of the dosing interval [Ctau]) were slightly lower than adults, but were markedly higher than the half-maximal inhibitory concentration. In children (aged 6 to <12 years), bictegravir AUCtau and Cmax values were modestly higher than those of adults and Ctau levels were similar to those of adults. Adherence was high and consistent with the acceptability of the tablet.
Implications of all the available evidence
The pharmacokinetics, safety, and tolerability of coformulated bictegravir, emtricitabine, and tenofovir alafenamide given as a single-tablet regimen in children and adolescents with HIV (aged 6 to <18 years with bodyweight ≥25 kg) informed the US Food and Drug Administration approval for this group in the USA. The findings of this study support ongoing paediatric drug development of this treatment regimen at lower doses for younger children.