Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years

Sharon Nachman, Nan Zheng, Edward P. Acosta, Hedy Teppler, Brenda Homony, Bobbie Graham, Terence Fenton, Xia Xu, Larissa Wenning, Stephen A. Spector, Lisa M. Frenkel, Carmelita Alvero, Carol Worrell, Edward Handelsman, Andrew Wiznia, Harry Moultrie, Gurpreet Kindra, Margaret Ann Sanders, Ruth Williams, Jennifer JensenMidnela Acevedo, Lizbeth Fabregas, Andrea Jurgrau, Marc Foca, Alice Higgins, Jaime G. Deville, Karin Nielsen-Saines, Michele F. Carter, John Swetnam, Joan Wilson, Margaret Donnelly, Siham Akleh, Mona Rigaud, Aditya Kaul, Nehali Patel, Aditya Gaur, L. Jill Utech, Edmundo Cardoso, Ana Maria Moreira, Breno Santos, Raziya Bobat, Rosie Mngqibisa, Marlene Burey, Jacob Abadi, Michael Rosenberg, Katherine Luzuriaga, Donna Picard, Jessica Pagano-Therrien, Sylvia Dittmer, Hilda Ntatule Ndiweni, Amisha Patel, Michelle Delrey, Chivon McMullen-Jackson, Mary E. Paul, Ann Melvin, Corry Venema-Weiss, Jenna Lane, Christy Beneri, Denise Ferraro, Erin Infanzon, James B. McAuley, Mariam Aziz, Maureen McNichols, Stephen Pelton, Deb McLaud, Diana Clarke, Steven Zeichner, Arezou Akar, Deidre Thompson, Steven D. Douglas, Richard M. Rutstein, Carol A. Vincent, Mary Elizabeth Vachon, Martha Cavallo, Murli Udharam Purswani, Gaerolwe Masheto, Anthony Ogwu, Tebogo Kakhu, Rolando M. Viani, Anita Darcey, Kimberly Norris, Sandra K. Burchett, Catherine Kneut, Nancy Karthas, Denise Casey, Patricia Emmanuel, Jorge Lujan-Zilbermann, Sohail Rana, Patricia Houston, Mulu Mengistab, Mobeen Rathore, Ayesha Mirza, Tabetha Gayton, Emily Barr, Jennifer Dunn, Kerry Hahn, Zulma Eysallenne, F. Sholar Howard, Kathleen Graham, Marinella Della Negra, Wladimir Queiroz, Yu Ching Lian, Diane Wara, Ted Ruel, Russell Vandyke, Patricia Reilly, Sheila Bradford, Anita Janse Van Rensburg, Els Dobbels, Marietjie Bester, Mahrukh Bamji, Santa Paul, Mirala Sarza, Andrea Kovacs, James Homans, Lashonda Spencer, Cristna Hofer, Thalita Abreu, Ricardo Oliveira, Esau C. Joao, Jorge Pinto, Flavia Ferreira, Fabiana Kakehasi, Maria Celia Cervi, Marcia De Lima Isaac, Marcelo H. Losso, Erica Stankievich, Irene Foradori, Diane Tucker, Joseph Church, Marvin Belzer, Johns Hopkins, Jonathan Ellen, Allison Agwu, Borkovic Laurel

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Background. IMPAACT P1066 is a phase I/II open-label multicenter trial to evaluate pharmacokinetics, safety, tolerability, and efficacy of multiple raltegravir formulations in human immunodeficiency virus (HIV)-infected youth.Methods. Dose selection for each cohort (I: 12 to <19 years; II: 6 to <12 years; and III: 2 to <6 years) was based on review of short-term safety (4 weeks) and intensive pharmacokinetic evaluation. Safety data through weeks 24 and 48, and grade ≥3 or serious adverse events (AEs) were assessed. The primary virologic endpoint was achieving HIV RNA <400 copies/mL or ≥1 log10 reduction between baseline and week 24.Results. The targeted pharmacokinetic parameters (AUC0-12h and C12h) were achieved for each cohort, allowing dose selection for 2 formulations. Of 96 final dose subjects, there were 15 subjects with grade 3 or higher clinical AEs (1 subject with drug-related [DR] psychomotor hyperactivity and insomnia); 16 subjects with grade 3 or higher laboratory AEs (1 with DR transaminase elevation); 14 subjects with serious clinical AEs (1 with DR rash); and 1 subjects with serious laboratory AEs (1 with DR transaminase increased). There were no discontinuations due to AEs and no DR deaths. Favorable virologic responses at week 48 were observed in 79.1% of patients, with a mean CD4 increase of 156 cells/μL (4.6%).Conclusions. Raltegravir as a film-coated tablet 400 mg twice daily (6 to <19 years, and ≥25 kg) and chewable tablet 6 mg/kg (maximum dose 300 mg) twice daily (2 to <12 years) was well tolerated and showed favorable virologic and immunologic responses.

Original languageEnglish (US)
Pages (from-to)413-422
Number of pages10
JournalClinical Infectious Diseases
Volume58
Issue number3
DOIs
StatePublished - Feb 2014

Keywords

  • adverse event
  • pediatric HIV
  • pharmacokinetics
  • raltegravir

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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