172. Safety and Efficacy of Dolutegravir (DTG; GSK1349572) in Treatment-Experienced HIV-1 Infected Adolescents: 24-Week Results from IMPAACT P1093
Session: Poster Abstract Session: ART: Efficacy and Resistance
Thursday, October 3, 2013
Room: The Moscone Center: Poster Hall C
  • P1093 PosterIDWeek PDF Cohort I 2013.pdf (159.6 kB)
  • Background: P1093 is an ongoing Phase I/II multicenter open-label PK, safety, dose finding study of DTG plus optimized background regimen (OBR) in children and adolescents in age defined cohorts. The pediatric weight band dosing of ~1 mg/kg once a day achieved PK exposure in adolescents comparable to those observed at 50 mg once daily in adults.

    Methods: HIV infected treatment experienced children >12 to < 18 yrs on a failing antiretroviral (ARV) regimen with an HIV RNA of ≥1000 copies/mL (c/mL) were enrolled in Stage 1 (intensive PK) or Stage 2 (extended follow up). DTG was added to a stable, failing ARV regimen in Stage 1, with an OBR added after intensive PK (~Day5-10), or DTG was started with an OBR in Stage 2. Safety, tolerability, CD4 cell count and HIV-1 RNA were evaluated at Week 24. Virologic success was defined as achieving an HIV-1 RNA < 400 c/mL by Week 24 based on the FDA snapshot algorithm, with an additional secondary endpoint of HIV-1 RNA <50 c/mL.

    Results: Twenty three adolescents (Stage 1, n=10; Stage 2, n=13) were enrolled and completed the 24 week study visit. Demographics were as follows: 78% (18/23) female, 52% (12/23) African American, 35% (8/23) Caucasian, 26% (6/23) were of Hispanic ethnicity. Mean (SD) age 14 yrs (±1.8) and weight= 55.1 kg (±15.6). Median (IQR) baseline CD4+ cell count and % were 466 cells/µL (297, 771) and 22% (18.4, 29.2) respectively. Median (IQR) baseline HIV-1 RNA log10 was 4.3 log10 c/mL (3.9, 4.6). Virologic success with an HIV RNA < 400 c/mL was achieved in 82.6 % (19/23 ; 95% CI: 61.2 % to 95%) at Week 24. Additionally, 69.6% (16/23 ; 95% CI: 47.1% to 86.8%) had an HIV RNA load < 50 c/mL at Week 24. Median (IQR) gain in CD4 cell count and % at Week 24 was 63 cells/µL (-56, 180) and 4.9% (1, 8) respectively. DTG was well tolerated, with 2 subjects experiencing Grade 3 laboratory abnormalities; one developed unconjugated bilirubin elevation while on atazanavir as part of the OBR, and another subject developed asymptomatic lipase elevation, which was deemed treatment unrelated. There were no Grade 4 AEs, SAEs or discontinuations due to AEs.

    Conclusion: DTG plus OBR was safe and well tolerated in HIV infected adolescents. In addition, DTG treatment as part of an OBR provided high virologic efficacy through Week 24.

    Rolando M. Viani, M.D.1, Nan Zheng2, Carmelita Alvero2, Rohan Hazra3, Ellen Townley O'gara4, Liz Petzold5, Barbara Heckman6, Debra Steimers7, Sherene Min7 and Andrew Wiznia, MD8, (1)Pediatrics, University of California, San Diego, La Jolla, CA, (2)Harvard School of Public Health, Boston, MA, (3)National Institute of Child Health and Human Development, Bethesda, MD, (4)HJF/DAIDS/NIAID/NIH, Bethesda, MD, (5)Social and Scientific Systems, Inc., Durham, NC, (6)Frontier Science and Technology Res Foundation, Amherst, NY, (7)GlaxoSmithKline, Research Triangle Park, NC, (8)Pediatrics/HIV, Jacobi Medical Center, Bronx, NY


    R. M. Viani, None

    N. Zheng, None

    C. Alvero, None

    R. Hazra, None

    E. Townley O'gara, None

    L. Petzold, None

    B. Heckman, None

    D. Steimers, GlaxoSmithKline: Employee, Salary

    S. Min, GlaxoSmithKline: Employee, Salary

    A. Wiznia, None

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