Pharmacokinetics and safety of maraviroc in neonates
| Autor: | Christina A Reding, Julia C. Rosebush, William Murtaugh, Elizabeth Smith, Sisinyana Ruth Mathiba, Impaact Study Team, Manoli Vourvahis, Pearl Samson, Mark Mirochnick, Ellen G Chadwick, Katy Hayward, Brookie M. Best, Lynn McFadyen, Edward P. Acosta, Mariam Aziz, Kevin Butler, Sherika Hanley, John Moye, James Homans, Sarah Bradford |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine maraviroc HIV Infections Medical and Health Sciences Cohort Studies Maraviroc chemistry.chemical_compound 0302 clinical medicine Open label study Immunology and Allergy Medicine 030212 general & internal medicine Pediatric Gestational age Biological Sciences Infectious Diseases Anti-Retroviral Agents 6.1 Pharmaceuticals Toxicity Cohort HIV/AIDS Female Infection pharmacokinetics Adult medicine.medical_specialty Efavirenz Clinical Trials and Supportive Activities antiretroviral Immunology Article 03 medical and health sciences Pharmacokinetics Clinical Research Cyclohexanes Virology Internal medicine Humans IMPAACT 2007 Study Team business.industry Psychology and Cognitive Sciences Infant Newborn Infant Evaluation of treatments and therapeutic interventions HIV Perinatal Period - Conditions Originating in Perinatal Period Newborn Design phase 030104 developmental biology chemistry HIV-1 neonate business |
| Zdroj: | AIDS AIDS (London, England), vol 35, iss 3 |
| ISSN: | 1473-5571 0269-9370 |
| DOI: | 10.1097/qad.0000000000002762 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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