Julia C. RosebushBrookie M. BestEllen G. ChadwickKevin ButlerJohn MoyeElizabeth SmithSarah BradfordChristina A. RedingSisinyana R. MathibaSherika HanleyMariam AzizJames HomansEdward P. AcostaWilliam MurtaughManoli VourvahisLynn McFadyenKaty HaywardMark MirochnickPearl SamsonNtatule Hilda NdiweniZaakirah EssackMandisa NyatiLorna PillayRosemary GazuNatasha PillayDamien SookooKulkanya ChokephaibulkitSupattra RungmaitreeKeswadee LapphraOrasri WittawatmongkolIsaac TsikhutsuEdner OpendaPriscillah BiiDavid WekuloEllen ChadwickJessica D’AngeloMargaret Ann SandersAlice StekMikhaela CieloLa Shonda SpencerYvonne MoralesChristiana Smith-AndersonKacey NavarroCarrie GlennyElizabeth McFarlandR. N. Maureen McNicholsJulie SchmidtHelen CejtinIxchell Ortiz-EstesKatherine KnappNehali PatelPatricia M. FlynnJill UtechKathleen GeorgeShane ReynoldsTerence FentonMichelle HsuJamie Branco-RicardVictoria WongBarbara HeckmanKyle WhitsonShawn WardNavdeep K. ThooferSiriraj HospitalFHI 360ViiV HealthcarePfizer Limited, UKFrontier Science & Technology Research Foundation, Inc.Kenya Medical Research InstituteHarvard T.H. Chan School of Public HealthUniversity of California, San DiegoUniversity of Southern CaliforniaThe University of ChicagoThe University of Alabama at BirminghamChildren's Hospital Los AngelesSt. Jude Children's Research HospitalBoston UniversityRush University Medical CenterNational Institute of Allergy and Infectious Diseases (NIAID)Ann & Robert H. Lurie Children's Hospital of ChicagoUniversity of the Witwatersrand, JohannesburgUniversity of KwaZulu-NatalNational Institutes of Health (NIH)Rush UniversityIMPAACT Statistical and Data Analysis CenterIMPAACT Data Management CenterIMPAACT Laboratory CenterCAPRISA Umlazi Clinical Research SiteIMPAACT Operations CenterUniversity of ColoradoAnn and Robert H. Lurie Children's Hospital of ChicagoEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentPfizer Global Research and Development2022-08-042022-08-042021-03-01AIDS. Vol.35, No.3 (2021), 419-42714735571026993702-s2.0-85101896085https://repository.li.mahidol.ac.th/handle/20.500.14594/77322Objective: The aim of this study was to evaluate safety and pharmacokinetics of maraviroc administered with standard antiretroviral prophylaxis to HIV-1 exposed infants and to determine the appropriate dose of maraviroc during the first 6 weeks of life. Design: A phase I, multicentre, open-label study enrolling two sequential cohorts. Methods: IMPAACT 2007 participants enrolled by day 3 of life and were stratified by exposure to maternal efavirenz. Cohort 1 participants received two single 8 mg/kg maraviroc doses 1 week apart with pharmacokinetic sampling after each dose. Cohort 2 participants received 8 mg/kg maraviroc twice daily through 6 weeks of life with pharmacokinetic sampling at weeks 1 and 4. Maraviroc exposure target was Cavg at least 75 ng/ml. Laboratory and clinical evaluations assessed safety. Results: Fifteen Cohort 1 and 32 Cohort 2 HIV-exposed neonates were enrolled (median gestational age 39 weeks, 51% male). All 13 evaluable Cohort 1 infants met the pharmacokinetic target. Median exposure for the 25 evaluable Cohort 2 infants met the pharmacokinetic target but variability was high, with 17–33% of infants below target at Weeks 1 and 4. Pharmacokinetic target achievement was similar between efavirenz exposure strata. No Grade 3þ toxicities, early study or treatment discontinuations due to maraviroc occurred. Conclusion: Median maraviroc exposure met the Cavg target in neonates receiving 8 mg/kg twice daily, although exposures were variable. Maternal efavirenz use did not impact maraviroc exposure and no discontinuations were due to maraviroc toxicity/ intolerance. No infants acquired HIV-1 infection during follow-up. Maraviroc 8 mg/kg twice daily appears well tolerated during the first 6 weeks of life.Mahidol UniversityImmunology and MicrobiologyMedicineArticleSCOPUS10.1097/QAD.0000000000002762