Tenofovir alafenamide exposure is modestly higher in children than adults

Tenofovir alafenamide (TAF) and its metabolite tenofovir (TFV) exposures are slightly higher in children aged 6-12 years compared with adults, according to data presented at CROI 2017.

The original tenofovir formulation, tenofovir disoproxil fumarate (TDF) is not a recommended first-line nucleos(t)ide reverse transcriptase inhibitor in children. This is due to its association with bone and renal toxicity – linked to plasma exposure. TAF provides 91% lower TFV exposure than TDF and is considered to have better renal and bone safety in adults and adolescents. There is interest in the potential benefits of TAF for paediatric HIV.

TAF is currently commercially available for adults and adolescents from the originator manufacturer (Gilead Sciences) within fixed dose combinations (FDC) and co-formulations, which are under investigation for children.

The company showed 24 week findings from a pharmacokinetic (PK), safety and efficacy study of the once daily FDC elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF) 150/150/200/10 mg, which is approved for adults and adolescents aged 12 and above.

The study was a phase 2/3, single-arm, open-label, 48 week, switch trial. Eligible children were aged 6-12 years, weighing at least 25 kg and virologically suppressed (<50 copies/mL) on stable antiretroviral therapy (ART) for six months or more.

PK assessments were made on all the agents in the FDC, as well as TFV, at steady state. These were compared with adult values. Adverse events (AE), laboratory tests, including viral load, were also conducted. Bone mineral density (BMD) z-score was assessed every 24 weeks

The study enrolled 23 children: median age 10 years (range 8 to 11), median weight 31 kg (range 26 to 58), 14 (61%) female, 18 (78%) black, median CD4 count 969 cells/mm3 (range 603 to 1421).

At 24 weeks mean AUCtau were 333 h*ng/mL (45% coefficient of variation) and 440 (21% coefficient of variation) for TAF and TFV respectively. These were modestly higher than adult values, but within safe and efficacious ranges of adults. Exposures of the other agents in the FDC followed a similar pattern.

No child had a serious AE or one leading to study drug discontinuation. No child had proximal renal tubulopathy. Median per cent change in BMD at 24 weeks was +4.2% for spine and +1.2% for total body less head Median change in BMD height-adjusted z-score was +0.10 for spine and -0.12 for TBLH.