Pharmacokinetics and safety of maraviroc in neonates.
Julia C Rosebush, Brookie M Best, Ellen G Chadwick, Kevin Butler, John Moye, Elizabeth Smith, Sarah Bradford, Christina A Reding, Sisinyana R Mathiba, Sherika Hanley, Mariam Aziz, James Homans, Edward P Acosta, William Murtaugh, Manoli Vourvahis, Lynn Mcfadyen, Katy Hayward, Mark Mirochnick, Pearl Samson, for the IMPAACT 2007 Study Team
AIDS (London, England) 2021 Mar 01The 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. A phase I, multicentre, open-label study enrolling two sequential cohorts. 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. 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 3+ toxicities, early study or treatment discontinuations due to maraviroc occurred. 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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Citation
Julia C Rosebush, Brookie M Best, Ellen G Chadwick, Kevin Butler, John Moye, Elizabeth Smith, Sarah Bradford, Christina A Reding, Sisinyana R Mathiba, Sherika Hanley, Mariam Aziz, James Homans, Edward P Acosta, William Murtaugh, Manoli Vourvahis, Lynn Mcfadyen, Katy Hayward, Mark Mirochnick, Pearl Samson, for the IMPAACT 2007 Study Team. Pharmacokinetics and safety of maraviroc in neonates. AIDS (London, England). 2021 Mar 01;35(3):419-427
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PMID: 33252481
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