Publication:
Pharmacokinetics and safety of maraviroc in neonates

Issued Date

2021-03-01

Resource Type

Article

ISSN

14735571
02699370

DOI

10.1097/QAD.0000000000002762

Other identifier(s)

2-s2.0-85101896085

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

AIDS. Vol.35, No.3 (2021), 419-427

Suggested 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, Ntatule Hilda Ndiweni, Zaakirah Essack, Mandisa Nyati, Lorna Pillay, Rosemary Gazu, Natasha Pillay, Damien Sookoo, Kulkanya Chokephaibulkit, Supattra Rungmaitree, Keswadee Lapphra, Orasri Wittawatmongkol, Isaac Tsikhutsu, Edner Openda, Priscillah Bii, David Wekulo, Ellen Chadwick, Jessica D’Angelo, Margaret Ann Sanders, Alice Stek, Mikhaela Cielo, La Shonda Spencer, Yvonne Morales, Christiana Smith-Anderson, Kacey Navarro, Carrie Glenny, Elizabeth McFarland, R. N. Maureen McNichols, Julie Schmidt, Helen Cejtin, Ixchell Ortiz-Estes, Katherine Knapp, Nehali Patel, Patricia M. Flynn, Jill Utech, Kathleen George, Shane Reynolds, Terence Fenton, Michelle Hsu, Jamie Branco-Ricard, Victoria Wong, Barbara Heckman, Kyle Whitson, Shawn Ward, Navdeep K. Thoofer Pharmacokinetics and safety of maraviroc in neonates. AIDS. Vol.35, No.3 (2021), 419-427. doi:10.1097/QAD.0000000000002762 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/77322

Research Projects

Organizational Units

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Journal Issue

Thesis

Title

Pharmacokinetics and safety of maraviroc in neonates

Author(s)

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
 Ntatule Hilda Ndiweni
 Zaakirah Essack
 Mandisa Nyati
 Lorna Pillay
 Rosemary Gazu
 Natasha Pillay
 Damien Sookoo
 Kulkanya Chokephaibulkit
 Supattra Rungmaitree
 Keswadee Lapphra
 Orasri Wittawatmongkol
 Isaac Tsikhutsu
 Edner Openda
 Priscillah Bii
 David Wekulo
 Ellen Chadwick
 Jessica D’Angelo
 Margaret Ann Sanders
 Alice Stek
 Mikhaela Cielo
 La Shonda Spencer
 Yvonne Morales
 Christiana Smith-Anderson
 Kacey Navarro
 Carrie Glenny
 Elizabeth McFarland
 R. N. Maureen McNichols
 Julie Schmidt
 Helen Cejtin
 Ixchell Ortiz-Estes
 Katherine Knapp
 Nehali Patel
 Patricia M. Flynn
 Jill Utech
 Kathleen George
 Shane Reynolds
 Terence Fenton
 Michelle Hsu
 Jamie Branco-Ricard
 Victoria Wong
 Barbara Heckman
 Kyle Whitson
 Shawn Ward
 Navdeep K. Thoofer

Other Contributor(s)

Siriraj Hospital
 FHI 360
 ViiV Healthcare
 Pfizer Limited, UK
 Frontier Science & Technology Research Foundation, Inc.
 Kenya Medical Research Institute
 Harvard T.H. Chan School of Public Health
 University of California, San Diego
 University of Southern California
 The University of Chicago
 The University of Alabama at Birmingham
 Children's Hospital Los Angeles
 St. Jude Children's Research Hospital
 Boston University
 Rush University Medical Center
 National Institute of Allergy and Infectious Diseases (NIAID)
 Ann & Robert H. Lurie Children's Hospital of Chicago
 University of the Witwatersrand, Johannesburg
 University of KwaZulu-Natal
 National Institutes of Health (NIH)
 Rush University
 IMPAACT Statistical and Data Analysis Center
 IMPAACT Data Management Center
 IMPAACT Laboratory Center
 CAPRISA Umlazi Clinical Research Site
 IMPAACT Operations Center
 University of Colorado
 Ann and Robert H. Lurie Children's Hospital of Chicago
 Eunice Kennedy Shriver National Institute of Child Health and Human Development
 Pfizer Global Research and Development

Abstract

Objective: 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.

Keyword(s)

Immunology and Microbiology
 Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/77322

Collections

Scopus 2021