Few antiretroviral options exist for smaller children living with HIV and no single-tablet regimen (STR) is used or approved for this population. STR of bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) is approved for use in HIV-infected children weighing ≥25 kg. We report safety, pharmacokinetics (PK), and efficacy from an interim analysis of the first clinical trial of a low dose B/F/TAF tablet in young children living with HIV.
Virologically suppressed children (≥2 yrs) weighing 14 to <25 kg with HIV-1 RNA <50 c/mL for ≥6 months and CD4 ≥200 cells/μL at screening, received low dose B/F/TAF (30/120/15 mg) once daily in a prospective, 48-week (W), single-arm, open-label trial. Adverse events (AE), laboratory tests, and the proportion of participants with HIV-1 RNA <50 c/mL were assessed through W12. Steady-state PK of B/F/TAF was evaluated; BIC PK in children were compared to B/F/TAF-treated adults (50/200/25 mg) using a 50-200% equivalence boundary.
Twelve children were enrolled; median age 6 (range 3-9) years, median weight 20.1 (range 14.6-24.1) kg, 58% female, 58% black, median CD4 count 841 cells/μL, all vertically infected. Through a median (Q1, Q3) duration of exposure to study drug of 20.1 (18.0, 27.1) weeks, most common AEs were abdominal pain, diarrhea, and upper respiratory tract infection (n=2 participants each); all AEs were grade 1 or 2; no child discontinued STR for AE. Related-AEs included neutropenia, irritability, and social avoidant behavior (n=1 each). Mean (SD) adherence to study drug was high (97.1% [7.02]). Ten of 11 (91%) children had HIV-1 RNA <50 c/mL at W12. Mean increase in CD4 count from baseline was 42 cells/mL. Geometric least squares mean ratios and 90% CIs for BIC AUCtau and Cmax in children vs adults were within 50-200%; BIC Ctau was 32% lower (Table). FTC and TAF exposures were within the range of historical data.
The B/F/TAF pediatric STR had high levels of adherence and virologic suppression. Exposures of all B/F/TAF drug components in young children were in the range of older populations, with mean BIC Ctau 12-fold above the paEC95 for wild type virus. Efficacy and safety of the pediatric STR in young children are consistent with adult strength STR efficacy in older populations. These data support further evaluation of low dose B/F/TAF as an unboosted INSTI-based STR for young children living with HIV.