Safety, Pharmacokinetics And Efficacy Of Dolutegravir In Treatment-Experienced Hiv-1 Infected Adolescents Forty-Eight-Week Results From Impaact P1093

Objective: To assess the pharmacokinetics (PK), safety and efficacy of dolutegravir plus optimized background regimen in HIV-infected treatment-experienced adolescents.Methods: Children older than 12 to younger than 18 years received dolutegravir weight-based fixed doses at approximately 1.0mg/kg once daily in a phase I/II multicenter open label 48-week study. Intensive PK evaluation was done at steady state after dolutegravir was added to a failing regimen or started at the end of a treatment interruption. Safety and HIV RNA and CD4 cell count assessments were performed through week 48.Results: Twenty-three adolescents were enrolled and 22 (96%) completed the 48-week study visit. Median age and weight were 15 years and 52kg, respectively. Median [interquartile range (IQR)] baseline CD4+ cell count was 466 cells/L (297, 771). Median (IQR) baseline HIV-1 RNA log(10) was 4.3 log(10) copies/mL (3.9, 4.6). Dolutegravir geometric mean of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing (AUC(0-24)) and 24 hour postdose concentration (C-24) were 46.0 g hours/mL and 0.90 g/mL, respectively, which were within the study targets based on adult PK ranges. Virologic success with an HIV RNA <400 copies/mL was achieved in 74% [95% confidence interval (CI): 52-90%] at week 48. Additionally, 61% (95% CI: 39-80%) had an HIV RNA <50 copies/mL at week 48. Median (IQR) gain in CD4 cell count at week 48 was 84 cells/L (-81, 238). Dolutegravir was well tolerated, with no grade 4 adverse events, serious adverse events or discontinuations because of serious adverse events.Conclusions: Dolutegravir achieved target PK exposures in adolescents. Dolutegravir was safe and well tolerated, providing good virologic efficacy through week 48.