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Safety and Efficacy of E/C/F/TAF in HIV-1Infected Treatment-Naïve Adolescents
Aditya Gaur1; Hilda Kizito2; Rana Chakraborty3; Jagmohan Batra4; Pope Kosalaraksa5; Wicharn Luesomboon6; Yongwu Shao7; Devi SenGupta7; Martin S. Rhee7; Erin Quirk8
1St Jude Children's Rsr Hosp, Memphis, TN, USA;2Joint Clinical Rsr Cntr, Kampala, Uganda;3Emory Univ, Atlanta, GA, USA;4Miller Children's Hosp, Long Beach, CA, USA;5Khon Kaen Univ, Khon Kaen, Thailand;6Queen Savang Vadhana Memorial Hosp, Chon Buri, Thailand;7Gilead Scis, Inc, Foster City, CA, USA;8Gilead Sciences, Foster City, CA, USA
A subset of Tenofovir DF (TDF) recipients may have renal and bone toxicities. Tenofovir alafenamide (TAF), a novel prodrug of tenofovir shows 91% lower plasma tenofovir levels compared to TDF. In phase 3 adult studies, a single tablet regimen of elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg and TAF 10mg (E/C/F/TAF) was highly efficacious and well-tolerated, with improved renal and bone safety profiles as compared to TDF-containing regimens. We previously reported favorable pharmacokinetics of E/C/F/TAF in HIV-1 infected treatment-naïve adolescents through Week 24 and now report the safety and efficacy through the preplanned secondary efficacy endpoint at 48 weeks.
Treatment-naïve adolescents (12 to <18 years) with CD4 > 100 cells/mm3, weighing ≥35 kg received open-label E/C/F/TAF for 48 weeks. The primary efficacy endpoint was virologic success (HIV-1 RNA <50 c/mL) at Week 24 using the snapshot algorithm. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry.
50 adolescents enrolled and two discontinued prior to Week 48. At Week 48, 46/50 (92%) had HIV-1 RNA < 50 copies/mL. The mean (SD) increase in CD4 cell count was 224 (170) cells/μL. No subject developed antiretroviral resistance. The most commonly reported adverse events (AEs) were mild/moderate and unrelated to study treatment. No subjects discontinued study drug due to AE, and none had proximal renal tubulopathy. The median (Q1, Q3) change in serum creatinine (Cr) was +0.07 (0.02, 0.15) mg/dL, consistent with the inhibition of renal tubular Cr secretion by cobicistat. The median (Q1, Q3) percent change from baseline to week 48 in urine protein to Cr ratio, retinol binding protein to Cr ratio, and beta-2-microglobulin to Cr ratio were -27% (-55%, +19%), -22% (-46%, +22%), and -29% (-60%, -4%), respectively. The median (Q1, Q3) change in spine BMD was +3.3% (+0.8%, +7.1%) and that of total body less head (TBLH) BMD was +0.9% (-0.5%, +2.6%). The median (Q1, Q3) change in height-adjusted spine Z-score was -0.03 (-0.16, +0.20) and that of TBLH Z-score was -0.09 (-0.3, +0.07). One subject had a ≥4% decrease in spine BMD from baseline, and none had a TBLH BMD decrease of ≥4%.
E/C/F/TAF is an effective first-line therapy and is well-tolerated with favorable renal and bone safety profiles in HIV-1 infected adolescents. These findings support further evaluation of E/C/F/TAF in younger HIV-1 infected pediatric patients.