PMID- 24145879 OWN - NLM STAT- MEDLINE DCOM- 20140915 LR - 20211021 IS - 1537-6591 (Electronic) IS - 1058-4838 (Print) IS - 1058-4838 (Linking) VI - 58 IP - 3 DP - 2014 Feb TI - Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years. PG - 413-22 LID - 10.1093/cid/cit696 [doi] AB - 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/microL (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. CLINICAL TRIALS REGISTRATION: NCT00485264. FAU - Nachman, Sharon AU - Nachman S AD - Department of Pediatrics, State University of New York at Stony Brook. FAU - Zheng, Nan AU - Zheng N FAU - Acosta, Edward P AU - Acosta EP FAU - Teppler, Hedy AU - Teppler H FAU - Homony, Brenda AU - Homony B FAU - Graham, Bobbie AU - Graham B FAU - Fenton, Terence AU - Fenton T FAU - Xu, Xia AU - Xu X FAU - Wenning, Larissa AU - Wenning L FAU - Spector, Stephen A AU - Spector SA FAU - Frenkel, Lisa M AU - Frenkel LM FAU - Alvero, Carmelita AU - Alvero C FAU - Worrell, Carol AU - Worrell C FAU - Handelsman, Edward AU - Handelsman E FAU - Wiznia, Andrew AU - Wiznia A CN - International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1066 Study Team LA - eng SI - ClinicalTrials.gov/NCT00485264 GR - UL1 RR029890/RR/NCRR NIH HHS/United States GR - U01 AI068632/AI/NIAID NIH HHS/United States GR - UL1 RR024131/RR/NCRR NIH HHS/United States GR - U01 AI068616/AI/NIAID NIH HHS/United States GR - HHSN267200800001C/HD/NICHD NIH HHS/United States GR - U01 AI041110/AI/NIAID NIH HHS/United States GR - UL1 TR001082/TR/NCATS NIH HHS/United States GR - UL1 TR000423/TR/NCATS NIH HHS/United States GR - UL1 TR000038/TR/NCATS NIH HHS/United States GR - UM1 AI069456/AI/NIAID NIH HHS/United States GR - HHSN267200800001G/DK/NIDDK NIH HHS/United States GR - N01-DK-9-001/DK/NIDDK NIH HHS/United States GR - UL1 TR000161/TR/NCATS NIH HHS/United States GR - UM1 AI068632/AI/NIAID NIH HHS/United States GR - UM1 AI069463/AI/NIAID NIH HHS/United States GR - UM1 AI068616/AI/NIAID NIH HHS/United States GR - AI068632/AI/NIAID NIH HHS/United States GR - UL1 TR002319/TR/NCATS NIH HHS/United States GR - 1 U01 AI068616/AI/NIAID NIH HHS/United States GR - 5 U01 AI41110/AI/NIAID NIH HHS/United States GR - UM1 AI069536/AI/NIAID NIH HHS/United States GR - P30 AI050410/AI/NIAID NIH HHS/United States PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20131021 PL - United States TA - Clin Infect Dis JT - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JID - 9203213 RN - 0 (Anti-HIV Agents) RN - 0 (Pyrrolidinones) RN - 0 (RNA, Viral) RN - 43Y000U234 (Raltegravir Potassium) SB - IM MH - Administration, Oral MH - Adolescent MH - Anti-HIV Agents/*administration & dosage/*adverse effects MH - Child MH - Child, Preschool MH - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology MH - Female MH - HIV Infections/*drug therapy/virology MH - HIV-1/*isolation & purification MH - Humans MH - Infant MH - Male MH - Pyrrolidinones/*administration & dosage/*adverse effects MH - RNA, Viral/blood MH - Raltegravir Potassium MH - Treatment Outcome MH - Viral Load MH - Young Adult PMC - PMC3890333 OTO - NOTNLM OT - adverse event OT - pediatric HIV OT - pharmacokinetics OT - raltegravir FIR - Moultrie, Harry IR - Moultrie H FIR - Kindra, Gurpreet IR - Kindra G FIR - Sanders, Margaret Ann IR - Sanders MA FIR - Williams, Ruth IR - Williams R FIR - Jensen, Jennifer IR - Jensen J FIR - Acevedo, Midnela IR - Acevedo M FIR - Fabregas, Lizbeth IR - Fabregas L FIR - Jurgrau, Andrea IR - Jurgrau A FIR - Foca, Marc IR - Foca M FIR - Higgins, Alice IR - Higgins A FIR - Deville, Jaime G IR - Deville JG FIR - Nielsen-Saines, Karin IR - Nielsen-Saines K FIR - Carter, Michele F IR - Carter MF FIR - Swetnam, John IR - Swetnam J FIR - Wilson, Joan IR - Wilson J FIR - Donnelly, Margaret IR - Donnelly M FIR - Akleh, Siham IR - Akleh S FIR - Rigaud, Mona IR - Rigaud M FIR - Kaul, Aditya IR - Kaul A FIR - Patel, Nehali IR - Patel N FIR - Gaur, Aditya IR - Gaur A FIR - Utech, L Jill IR - Utech LJ FIR - Cardoso, Edmundo IR - Cardoso E FIR - Moreira, Ana Maria IR - Moreira AM FIR - Santos, Breno IR - Santos B FIR - Bobat, Raziya IR - Bobat R FIR - Mngqibisa, Rosie IR - Mngqibisa R FIR - Burey, Marlene IR - Burey M FIR - Abadi, Jacob IR - Abadi J FIR - Rosenberg, Michael IR - Rosenberg M FIR - Luzuriaga, Katherine IR - Luzuriaga K FIR - Picard, Donna IR - Picard D FIR - Pagano-Therrien, Jessica IR - Pagano-Therrien J FIR - Dittmer, Sylvia IR - Dittmer S FIR - Ndiweni, Hilda Ntatule IR - Ndiweni HN FIR - Patel, Amisha IR - Patel A FIR - Delrey, Michelle IR - Delrey M FIR - McMullen-Jackson, Chivon IR - McMullen-Jackson C FIR - Paul, Mary E IR - Paul ME FIR - Melvin, Ann IR - Melvin A FIR - Venema-Weiss, Corry IR - Venema-Weiss C FIR - Lane, Jenna IR - Lane J FIR - Beneri, Christy IR - Beneri C FIR - Ferraro, Denise IR - Ferraro D FIR - Infanzon, Erin IR - Infanzon E FIR - McAuley, James B IR - McAuley JB FIR - Aziz, Mariam IR - Aziz M FIR - McNichols, Maureen IR - McNichols M FIR - Pelton, Stephen IR - Pelton S FIR - McLaud, Deb IR - McLaud D FIR - Clarke, Diana IR - Clarke D FIR - Zeichner, Steven IR - Zeichner S FIR - Akar, Arezou IR - Akar A FIR - Thompson, Deidre IR - Thompson D FIR - Douglas, Steven D IR - Douglas SD FIR - Rutstein, Richard M IR - Rutstein RM FIR - Vincent, Carol A IR - Vincent CA FIR - Vachon, Mary Elizabeth IR - Vachon ME FIR - Cavallo, Martha IR - Cavallo M FIR - Purswani, Murli Udharam IR - Purswani MU FIR - Masheto, Gaerolwe IR - Masheto G FIR - Ogwu, Anthony IR - Ogwu A FIR - Kakhu, Tebogo IR - Kakhu T FIR - Viani, Rolando M IR - Viani RM FIR - Darcey, Anita IR - Darcey A FIR - Norris, Kimberly IR - Norris K FIR - Burchett, Sandra K IR - Burchett SK FIR - Kneut, Catherine IR - Kneut C FIR - Karthas, Nancy IR - Karthas N FIR - Casey, Denise IR - Casey D FIR - Emmanuel, Patricia IR - Emmanuel P FIR - Lujan-Zilbermann, Jorge IR - Lujan-Zilbermann J FIR - Rana, Sohail IR - Rana S FIR - Houston, Patricia IR - Houston P FIR - Mengistab, Mulu IR - Mengistab M FIR - Rathore, Mobeen IR - Rathore M FIR - Mirza, Ayesha IR - Mirza A FIR - Gayton, Tabetha IR - Gayton T FIR - Barr, Emily IR - Barr E FIR - Dunn, Jennifer IR - Dunn J FIR - Hahn, Kerry IR - Hahn K FIR - Eysallenne, Zulma IR - Eysallenne Z FIR - Howard, F Sholar IR - Howard FS FIR - Graham, Kathleen IR - Graham K FIR - Negra, Marinella Della IR - Negra MD FIR - Queiroz, Wladimir IR - Queiroz W FIR - Lian, Yu Ching IR - Lian YC FIR - Wara, Diane IR - Wara D FIR - Ruel, Ted IR - Ruel T FIR - Vandyke, Russell IR - Vandyke R FIR - Reilly, Patricia IR - Reilly P FIR - Bradford, Sheila IR - Bradford S FIR - van Rensburg, Anita Janse IR - van Rensburg AJ FIR - Dobbels, Els IR - Dobbels E FIR - Bester, Marietjie IR - Bester M FIR - Bamji, Mahrukh IR - Bamji M FIR - Paul, Santa IR - Paul S FIR - Sarza, Mirala IR - Sarza M FIR - Kovacs, Andrea IR - Kovacs A FIR - Homans, James IR - Homans J FIR - Spencer, Lashonda IR - Spencer L FIR - Hofer, Cristna IR - Hofer C FIR - Abreu, Thalita IR - Abreu T FIR - Oliveira, Ricardo IR - Oliveira R FIR - Joao, Esau C IR - Joao EC FIR - Pinto, Jorge IR - Pinto J FIR - Ferreira, Flavia IR - Ferreira F FIR - Kakehasi, Fabiana IR - Kakehasi F FIR - Cervi, Maria Celia IR - Cervi MC FIR - Isaac, Marcia De Lima IR - Isaac Mde L FIR - Losso, Marcelo H IR - Losso MH FIR - Stankievich, Erica IR - Stankievich E FIR - Foradori, Irene IR - Foradori I FIR - Tucker, Diane IR - Tucker D FIR - Church, Joseph IR - Church J FIR - Belzer, Marvin IR - Belzer M FIR - Hopkins, Johns IR - Hopkins J FIR - Ellen, Jonathan IR - Ellen J FIR - Agwu, Allison IR - Agwu A FIR - Laurel, Borkovic IR - Laurel B EDAT- 2013/10/23 06:00 MHDA- 2014/09/16 06:00 PMCR- 2015/02/01 CRDT- 2013/10/23 06:00 PHST- 2013/10/23 06:00 [entrez] PHST- 2013/10/23 06:00 [pubmed] PHST- 2014/09/16 06:00 [medline] PHST- 2015/02/01 00:00 [pmc-release] AID - cit696 [pii] AID - 10.1093/cid/cit696 [doi] PST - ppublish SO - Clin Infect Dis. 2014 Feb;58(3):413-22. doi: 10.1093/cid/cit696. Epub 2013 Oct 21.