Safety, Pharmacokinetics and Efficacy of Dolutegravir in Treatment-experienced HIV-1 Infected Adolescents: Forty-eight-week Results from IMPAACT P1093. Issue 11 (November 2015)

• Record Type: Journal Article
• Authors: Viani, Rolando M.; Alvero, Carmelita; Fenton, Terry; Acosta, Edward P.; Hazra, Rohan; Townley, Ellen; Steimers, Debra; Min, Sherene; Wiznia, Andrew
• Is Part Of: Pediatric infectious disease journal. Volume 34:Issue 11(2015)
• Publication Date: 2015-11
• Subjects: antiretroviral agents -- dolutegravir -- HIV integrase inhibitors -- pediatric HIV -- adolescent HIV; Communicable diseases in children -- Periodicals; Infection in children -- Periodicals; 618.929
• DOI: 10.1097/INF.0000000000000848
• Languages: English
• ISSNs: 0891-3668

Abstract

Abstract : 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 1.0 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. Results: Twenty-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 ( C 24 ) 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. Conclusions: Dolutegravir achieved target PK exposures in adolescents. Dolutegravir was safe and well tolerated, providing good virologic efficacy through week 48.