RESUMEN
OBJECTIVE: Limited pharmacokinetic/pharmacodynamic data are a barrier to the scale-up of dolutegravir-based antiretroviral therapy (ART) in children. We examined the pharmacokinetics/pharmacodynamics of the adult film-coated dolutegravir 50âmg tablets in children with HIV infection weighing at least 20âkg. DESIGN: A prospective, observational, pharmacokinetic, and safety study. METHODS: Treatment-experienced children with HIV weighing at least 20âkg and evidence of viral load suppression on ART were enrolled and switched to dolutegravir-based therapy. After at least 4âweeks and 7âmonths on dolutegravir-based therapy, blood samples were collected at 0, 1, 4, 8, 12, and 24-h postdose. Dolutegravir concentrations were measured using validated LCMS/MS and pharmacokinetic parameters calculated by noncompartmental analysis. Descriptive statistics were used to summarize pharmacokinetic parameters and comparisons with published reference values. RESULTS: Of 25 participants, 92% were on efavirenz-based ART and 60.0% were men. Dolutegravir mean exposure, peak and trough concentrations at both pharmacokinetic visits were higher than the mean reference values in adults and children weighing 20âkg to less than 40âkg treated with 50âmg once daily, but were closer to the mean values in adults given 50âmg twice a day. Children weighing 20âkg to less than 40âkg had even higher dolutegravir exposures. The regimens were well tolerated with good virologic efficacy through week 48. CONCLUSION: The higher dolutegravir exposure in our study population suggests that further studies and close monitoring should investigate the adverse effects of dolutegravir in more children and in the long term.