• Rolando M Viani, Carmelita Alvero, Terry Fenton, Edward P Acosta, Rohan Hazra, Ellen Townley, Debra Steimers, Sherene Min, Andrew Wiznia, and P1093 Study Team.
• From the *Department of Pediatrics, University of California, San Diego, California; †Rady Children's Hospital San Diego, La Jolla, California; ‡Statistical and Data Analysis Center, Harvard School Public Health, Boston, Massachusetts; §University of Alabama at Birmingham, Birmingham, Alabama; ¶Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; ‖HJF-DAIDS, A Division of the Henry Jackson Foundation, Contractor to the Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland; **GlaxoSmithKline, Research Triangle Park, North Carolina; and ††Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York.
• Pediatr. Infect. Dis. J. 2015 Nov 1; 34 (11): 1207-13.

ObjectiveTo assess the pharmacokinetics (PK), safety and efficacy of dolutegravir plus optimized background regimen in HIV-infected treatment-experienced adolescents.MethodsChildren older than 12 to younger than 18 years received dolutegravir weight-based fixed doses at approximately 1.0 mg/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.ResultsTwenty-three adolescents were enrolled and 22 (96%) completed the 48-week study visit. Median age and weight were 15 years and 52 kg, respectively. Median [interquartile range (IQR)] baseline CD4+ cell count was 466 cells/μL (297, 771). Median (IQR) baseline HIV-1 RNA log10 was 4.3 log10 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 (AUC0-24) and 24 hour postdose concentration (C24) were 46.0 μg hours/mL and 0.90 μg/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/μL (-81, 238). Dolutegravir was well tolerated, with no grade 4 adverse events, serious adverse events or discontinuations because of serious adverse events.ConclusionsDolutegravir achieved target PK exposures in adolescents. Dolutegravir was safe and well tolerated, providing good virologic efficacy through week 48.

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