Bictegravir (BIC), a novel, unboosted integrase strand transfer inhibitor (INSTI) with a high genetic barrier to resistance, has been coformulated with emtricitabine and tenofovir alafenamide (BIC/FTC/TAF; B/F/TAF) into a once daily, single-tablet regimen (STR) of small tablet size that can be taken with/without food. We report pharmacokinetics (PK), safety and efficacy from a planned interim analysis of the first clinical trial of B/F/TAF in HIV-infected adolescents.
Virologically suppressed adolescents (12 to <18 yrs) weighing ≥35 kg with HIV-1 RNA <50 c/mL for ≥6 months before screening and CD4 ≤200 cells/μL received B/F/TAF once daily in a prospective, 48-week (W), single-arm, open-label trial. Steady-state PK parameters in adolescents were compared to those observed in adults treated with B/F/TAF. Adverse events (AE), laboratory tests, and the proportion of subjects with HIV-1 RNA <50 c/mL were assessed through W24.
24 adolescents enrolled; median age 15 yrs (range 12-17 yrs), median weight 48.9 kg (range 36.1-88.6 kg), 79% female, 52% Black, median CD4 count 708 cells/μL, 88% vertically infected. All (100%) had HIV-1 RNA <50 c/mL at W24 and none met criteria for resistance testing. Mean change in CD4 count from baseline was 44 cells/μL. No clinically relevant differences in drug exposures of B/F/TAF components were observed compared with data from adults (Table). Through a median (Q1, Q3) duration of exposure to study drug of 25.6 (24.7, 26.6) weeks, the most common treatment emergent AE was upper respiratory tract infection (21%, 5 of 24); no other AE occurred in >2 participants. No subject discontinued for AE. All participants reported B/F/TAF size and shape to be acceptable, and mean (SD) adherence to study drug was high (97.1% [7.02]). µ µ
The B/F/TAF STR maintained virologic suppression in all adolescent subjects enrolled and was well-tolerated through 24 weeks. Similar to adults treated with B/F/TAF, therapeutic plasma concentrations of all components of B/F/TAF were achieved. The efficacy and safety in adolescents is consistent with phase 3 B/F/TAF results in adults, which showed high proportions with viral suppression and no resistance. These data support further pediatric studies of B/F/TAF, which may be an important unboosted INSTI option for HIV-infected adolescents and children due to its high barrier to resistance, small tablet size and lack of food requirement.