Fixed-dose combination emtricitabine (FTC)/tenofovir alafenamide (TAF) is approved for adolescents (US, EU) and a recommended first-line NRTI backbone for adolescents (US). Safety and efficacy of TAF in adolescents has been demonstrated in studies of elvitegravir/cobicistat/FTC/TAF, including favorable bone and renal safety. Safety, pharmacokinetics (PK), and efficacy of other FTC/TAF-containing regimens in adolescents have not been reported. We describe safety, PK and efficacy of FTC/TAF in combination with boosted or unboosted third antiretroviral (ARV) agents to adolescents.
This open-label, 2-part, 48-week (W) trial evaluated switching from 2 NRTIs to FTC/TAF while remaining on various third ARV agents (eg efavirenz or lopinavir/ritonavir). Virologically suppressed adolescents (12 to <18 yrs) weighing ≥35 kg were enrolled and given FTC/TAF 200/10 mg or 200/25 mg, with boosted or unboosted third ARVs, respectively. Adverse events (AE), laboratory tests (eg renal biomarkers) and bone mineral density (BMD) were assessed. Intensive PK was evaluated at W2. Efficacy was evaluated as proportion of adolescents with plasma HIV-1 RNA <50 copies(c)/mL (snapshot algorithm). We report safety, PK and efficacy through W24.
We treated 28 adolescents; median age 14 yrs (range 12-17), median weight 45 kg (range 35-62), 43% female, 43% Black. Median (Q1, Q3) duration of exposure to study drug was 76 (56, 129) wks. Mean study drug adherence was high (93%). Most common AE was viral upper respiratory infection (32%). Two participants had serious, unrelated AEs. Five had AEs related to study drug; none discontinued study drug due to an AE. Mean % change from baseline in BMD at W24 was +3.9% for spine and +2.2% for total body less head (TBLH). Mean change in BMD height-age adjusted Z-score was 0.00 for spine and -0.03 for TBLH. Mean (SD) estimated change in glomerular filtration rate was 2.0 (20.95) mL/min/1.73m2. No clinically relevant differences in TAF and tenofovir exposures were observed in adolescents v. adults (Table). Most (93%, 26/28) maintained HIV-1 RNA <50 c/mL.
FTC/TAF with boosted or unboosted third agents in HIV-infected adolescents 12 to <18 yrs had high adherence rates and was well tolerated, while demonstrating increased BMD over 24 weeks. Exposure of TAF was similar to adults. High rate of virologic suppression was maintained at W24. Findings support FTC/TAF as a safe and effective NRTI backbone in adolescents.