Population Pharmacokinetics of Dolutegravir in African Children: Results From the CHAPAS-4 Trial

Abstract

We characterized population pharmacokinetics in 42 African children receiving once-daily 25 mg (14 to <20 kg) or 50 mg (>20 kg) dolutegravir. Coadministration with emtricitabine and tenofovir alafenamide reduced dolutegravir bioavailability by 19.6% (95% confidence interval: 8.13%-30.8%) compared with zidovudine or abacavir with lamivudine. Nevertheless, concentrations remained above efficacy targets, confirming current dosing recommendations.

Keywords: HIV; children; dolutegravir; pharmacokinetic; population pharmacokinetics.

Figure 1.

Simulated dolutegravir exposure, area under the concentration curve 0–24 hours (AUC_{0–24 h}, left panel) and concentration at 24 hours (C_trough, right panel) for children taking dolutegravir with standard of care (SOC; white boxes) or emtricitabine/tenofovir alafenamide (FTC/TAF; gray boxes) in dose and formulation 25 mg dispersible tablet for children 14 to <20 kg and 50 mg film-coated tablet for children weighing more than 20 kg. The boxes represent the 25th, 50th, and 75th percentiles, while the whiskers show the 5th and 95th percentiles. The dashed line in the AUC panel indicates the adult geometric mean AUC_{0–24 h} of adults taking 50 mg dolutegravir film-coated tablet with food of 53.6 h·mg/L [8]. The dashed line in the C_trough panel indicates the reported 90% effective concentration (EC90) of 0.32 mg/L [9]. The dotted line in the C_trough panel indicates the in vitro protein-adjusted dolutegravir IC90 of 0.064 mg/L, the minimal target for efficacy.