Currently, no once-daily (QD) single-tablet regimen (STR) is available for HIV-infected children <12 years of age. Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF; E/C/F/TAF) is a QD integrase strand transfer inhibitor (INSTI)-based STR approved for use in adults and adolescents ≥12 years of age.
We conducted a prospective, single-arm, open-label, 2-part, 48-week clinical trial to evaluate the pharmacokinetics (PK), safety and efficacy of switching to the adult formulation of E/C/F/TAF (150/150/200/10 mg) QD in virologically suppressed children (6 to <12 years) weighing ≥25 kg. Intensive PK was evaluated and compared with adult values. Adverse events (AE), laboratory tests, including HIV-1 RNA, were assessed. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. We report intensive PK and follow up data through Week 24.
We enrolled 23 children; median age 10 y (range 8-11y), median weight 31 kg (range 25.5-58.2 kg), 61% female, 78% Black, median CD4 count 969 cells/μL. All (100%) had HIV-1 RNA <50 c/mL at Week 24. Plasma PK of EVG, COBI, FTC, and TAF (and its metabolite tenofovir) were modestly higher (20-80%) than in adults, but were within safe and efficacious ranges of adults. No subject had a serious AE or AE leading to study drug discontinuation. No subject had proximal renal tubulopathy. Estimated GFR (Schwartz formula) decreased at Week 4 and remained stable (median change at Week 24: -6.5 mL/min/1.73 m2), consistent with inhibition of renal tubular creatinine (Cr) secretion by COBI. Measures of proteinuria generally improved: median % change at Week 24 in urine protein to Cr ratio, retinol binding protein to Cr ratio, and beta-2-microglobulin to Cr ratio were -30%, -31%, and -6%, respectively. Median % change in BMD at Week 24 was +4.2% for spine and +1.2% for total body less head (TBLH). BMD decreases of ≥4% occurred in 2 subjects for spine and none for TBLH. Median change in BMD height-adjusted Z-score was +0.10 for spine and -0.12 for TBLH. No subject had a bone fracture.
In HIV-infected children 6 to <12 years of age, E/C/F/TAF uniformly maintained virologic suppression through Week 24. Using the adult formulation, plasma PK of all components were higher than adults; however, E/C/F/TAF was generally well tolerated through 24 weeks with a favorable renal and bone safety profile. These findings support use of E/C/F/TAF as the first QD and INSTI-based STR in children 6 to <12 years of age.