학술논문
Pharmacokinetics and safety of maraviroc in neonates.
Document Type
article
Author
Rosebush, Julia C; Best, Brookie M; Chadwick, Ellen G; Butler, Kevin; Moye, John; Smith, Elizabeth; Bradford, Sarah; Reding, Christina A; Mathiba, Sisinyana R; Hanley, Sherika; Aziz, Mariam; Homans, James; Acosta, Edward P; Murtaugh, William; Vourvahis, Manoli; Mcfadyen, Lynn; Hayward, Katy; Mirochnick, Mark; Samson, Pearl
Source
AIDS. 35(3)
Subject
Language
Abstract
ObjectiveThe 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.DesignA phase I, multicentre, open-label study enrolling two sequential cohorts.MethodsIMPAACT 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.ResultsFifteen 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.ConclusionMedian 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.