LAUSR

OBJECTIVE Limited pharmacokinetic/pharmacodynamic data are a barrier to the well tolerated scale-up of dolutegravir-based antiretroviral therapy (ART) in children. We examined the pharmacokinetic/pharmacodynamic of the adult film-coated dolutegravir 50 mg tablets in children with HIV infection weighing at least 20 kg. DESIGN A prospective, observational, pharmacokinetic, and safety study. METHODS Treatment-experienced children with HIV weighing at least 20 kg and evidence of viral load suppression on ART were enrolled and switched to dolutegravir-based therapy. After at least 4 weeks and 7 months 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 20 kg to less than 40 kg treated with 50 mg once daily, but were closer to the mean values in adults given 50 mg twice a day. Children weighing 20 kg to less than 40 kg 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.