409. Dose-Finding Pharmacokinetics (PK) and 24- and 48-Week Safety and Efficacy of Raltegravir (RAL) Granules for Suspension (GFS) Formulation in Human Immunodeficiency Virus Type-1 (HIV)-Infected Infants Starting Treatment at 4 Wk 6 Mo of Age
Session: Poster Abstract Session: Pediatric HIV
Thursday, October 3, 2013
Room: The Moscone Center: Poster Hall C
  • ID Week-P1066-RAL FINAL poster for ID Week-26sept2013.pdf (1.0 MB)
  • Background: Determine the dose of Raltegravir (RAL), an HIV integrase inhibitor, for infants 4wk-6mo of age. Evaluate safety, tolerance and efficacy of RAL given with optimized-background-therapy (OBT) after 24 and 48wk.

    Methods: Entry criteria allowed peripartum antiretroviral prophylaxis but no treatment and required HIV RNA >1000c/mL. RAL GFS dose was weight-based (~6 mg/kg Q12H). Intensive PK occurred between days 5-12. Dose selection PK targets were geometric mean [GM] AUC12hr 14-45 µM*h and GM C12hr ≥75 nM. Efficacy was defined as HIV RNA <400 copies/mL or ≥1 log drop from entry. Other efficacy parameters were RNA <50, RNA <400, log HIV RNA decline, and change in CD4 count and percent.

    Results: Subjects (n=12) were 67% male; 100% black. At enrollment age was 14.3wk (range 4-19); weight 5.4kg (range 3.4-7.3); and mean (SD) plasma HIV RNA 6.0 log10c/mL (1.2); CD4 18.4% (11.5%); CD4 1360 cells/uL (1004). Subjects received a mean RAL dose of 5.7 mg/kg Q12H. Their (n=11, one missing specimens) GM AUC12hr was 22.3 µM*h and the modeled GM C12hr was 116.6 nM, which achieved PK targets.  

    As of 7Feb2013, 2/12 subjects discontinued RAL; 1 due to rash (prior to the PK visit) and 1 for noncompliance with study visits; at analysis 4 subjects had not yet reached week 24. No subjects switched their OBT.  Adverse events (Grade ≥3) occurred in 2 infants; 1 rash considered possibly drug-related in a child with new onset PCP (not related), and 1 with gastroenteritis, diarrhea and hypovolemic shock (not related).

    Virologic and Immunologic Outcome after 24 and 48 weeks of RAL GFS

    Time point

    (# subjects)

    Mean ΔCD4 count from baseline

    Mean ΔCD4% from baseline

    % with Virologic success, (≥1 log10 drop from baseline or RNA<400)

    % with HIV RNA

    <400 / <50 copies/mL

    Mean log10 HIV RNA drop from Baseline

    Wk 24 (N=8)




    75% / 37.5%


    Wk 48 (N=8)




    67% / 50%


     Conclusion: Weight-based dosing of RAL GFS at ~6 mg/kg Q12H in subjects 4 wk-6mo of age achieved PK targets, was well tolerated, and achieved virologic success in most subjects. PK was similar to that observed in subjects 6 mo-2 yr of age, who also receiving RAL GFS at ~6 mg/kg Q12H. These data suggest that weight-based dosing of RAL GFS achieves targeted PK values, is generally safe, and well tolerated in HIV-infected young infants.

    Lisa Frenkel, MD, Seattle Children's Research Institute, Seattle, WA; Pediatrics, University of Washington, Seattle, WA, Sharon Nachman, MD, Pediatrics, HSC SUNY, Stony Brook, NY; SUNY School of Medicine, Stony Brook, NY; SUNY Stony Brook, Stony Brook, NY, Nan Zheng, Harvard School of Public Health, Boston, MA, Edward Acosta, PharmD, University of Alabama Birmingham, Birmingham, AL, Hedy Teppler, MD, Merck, Upper Gwynedd, PA, Carol Worrell, MD, NICHD, Bethesda, MD, Brenda Homony, MS, Merck Res Labs, Whitehouse Station, NJ, Stephen Spector, MD, University of California San Diego, San Diego, CA, Bobbie Graham, BS, Frontier Science and Technology Res. Foundation, Amherst, NY, Paul Sato, MD, MPH, Division of AIDS, NIAID, NIH, Bethesda, MD, Andrew Wiznia, MD, Pediatrics/HIV, Jacobi Medical Center, Bronx, NY and P1066 Study Team


    L. Frenkel, None

    S. Nachman, None

    N. Zheng, None

    E. Acosta, None

    H. Teppler, None

    C. Worrell, None

    B. Homony, None

    S. Spector, None

    B. Graham, None

    P. Sato, None

    A. Wiznia, None

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