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PHARMACOKINETICS, SAFETY & EFFICACY OF E/C/F/TAF IN HIV-INFECTED CHILDREN (6-12 YRS)
Aditya Gaur1, Eva Natukunda2, Pope Kosalarksa3, Jag Batra4, Natella Rakhmanina5, Amy Coluci6, Yongwu Shao6, Heather Zhang6, Cheryl Pikora6, Martin Rhee6
1St. Jude Children’s Rsr Hosp, Memphis, TN, USA,2Joint Clinical Rsr Cntr, Kampala, Uganda,3Khon Kaen Univ, Khon Kaen, Thailand,4Miller Children's Hosp, Long Beach, CA, USA,5Children's Rsr Inst–Children's Natl Med Cntr, Washington, DC, USA,6Gilead Scis, Inc, Foster City, CA, USA
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.