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. 2021 Mar 1;35(3):419-427.
doi: 10.1097/QAD.0000000000002762.

Pharmacokinetics and safety of maraviroc in neonates

Julia C Rosebush  1 , Brookie M Best  2 , Ellen G Chadwick  3 , Kevin Butler  4 , John Moye  5 , Elizabeth Smith  6 , Sarah Bradford  7 , Christina A Reding  8 , Sisinyana R Mathiba  9 , Sherika Hanley  10 , Mariam Aziz  11 , James Homans  12 , Edward P Acosta  13 , William Murtaugh  14 , Manoli Vourvahis  15 , Lynn Mcfadyen  16 , Katy Hayward  17 , Mark Mirochnick  18 , Pearl Samson  4   8 ; for the IMPAACT 2007 Study Team
Affiliations

Pharmacokinetics and safety of maraviroc in neonates

Julia C Rosebush et al. AIDS. .

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 3+ 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.

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Figures

Figure 1A:
Figure 1A:
Plot of Median Plasma Maraviroc Concentration-Time (Semi-Log) for Cohort 1 (All Dose-Finding Evaluable Infants). Values below the Lower Limit of Quantification (<5.00 ng/mL) are set to 0.
Figure 1B:
Figure 1B:
Plot of Median Plasma Maraviroc Concentration-Time (Semi-Log) for Cohort 2 (All Dose-Finding Evaluable Infants). Values below the Lower Limit of Quantification (<5.00 ng/mL) are set to 0.
Figure 2A:
Figure 2A:
CAVG Summary of Cohort 1 PK Dose-Finding Evaluable Infants. CAVG calculated for Q12hr dosing.
Figure 2B:
Figure 2B:
CAVG Summary of Cohort 2 PK Dose-Finding Evaluable Infants. CAVG calculated for Q12hr dosing.
See this image and copyright information in PMC

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