Background:
Emtricitabine/tenofovir alafenamide (F/TAF) is a preferred component of the pediatric ART regimen in the US guidelines and is on the WHO priority list for HIV treatment in children. Despite the increased worldwide use of INSTI-based regimens, PIs remain an important class when constructing the ARV regimen for children. There are limited data on the pharmacokinetics (PK) of F/TAF with boosted PIs in young children. We studied PK, safety and efficacy in virologically supressed children ≥3y weighing 14 to < 25kg taking the once-daily low dose tablet of F/TAF (120/15mg) and cobicistat-boosted darunavir (DRV/c).
Methods:
Participants were enrolled in an open-label study evaluating F/TAF given with DRV/c (NCT02016924). The primary objective was to evaluate steady-state PK of DRV and TAF and safety of F/TAF and DRV/c. Participants had CD4 ≥200 cells/μL and estimated glomerular filtration rate ≥90 mL/min/1.73m2 at screening and received F/TAF for at least 48 weeks, with a possible extension phase. All participants participated in an intensive PK visit, with regular HIV-RNA, adverse events (AEs), and laboratory tests assessments throughout the study. Continuous variables are presented as median (Q1, Q3), and PK parameters as geometric mean.
Results:
Nine participants were enrolled from South Africa and Zimbabwe: age 4y (3, 6); 5 females. Baseline absolute and relative CD4 count were 1237 (844, 1490) cells/µL and 41% (35, 42). Duration of study drug exposure was 66 (63, 72) weeks. Steady state PK parameters for TAF, tenofovir (TFV) and DRV are presented in Table 1. At Week 24, 100% (7/7; missing=excluded analysis) had a viral load < 50 copies/mL, while CD4 percentage increased 0.8% (-1.4, 1.7). The only AEs observed in more than 1 participant were vomiting and anaemia. No participant experienced a Grade 3-4 AE. Creatinine remained within the normal range throughout follow-up, with an increase at W60 of 0.01 (-0.04, 0.09) mg/dL.
Conclusions:
F/TAF LDT given with DRV/c showed acceptable exposures of TAF, TFV, and DRV in young children ≥3y weighing 14 to < 25 kg. The rate of maintained viral suppression is consistent with that observed in adolescents and adults after 24 weeks of treatment. The regimen was well tolerated. The results support continuing evaluation of F/TAF as an NRTI backbone in combination with boosted PIs in younger children with HIV; tablets for oral suspension of F/TAF and cobicistat have been developed for evaluation.
Table 1. Pharmacokinetics Parameters (Median) for TAF, TFV, and DRV 