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Pharmacokinetics and safety of maraviroc in neonates

Julia C Rosebush1, Brookie M Best2, Ellen G Chadwick3

  • 1University of Chicago, Chicago, Illinois.

AIDS (London, England)
|November 30, 2020
PubMed

Insights

Maraviroc at 8 mg/kg twice daily is safe and effective for HIV-1 exposed infants, meeting pharmacokinetic targets without toxicity. This dosing regimen is well-tolerated in neonates during the first six weeks of life.

Area of Science:

  • Pediatric Infectious Diseases
  • Pharmacology and Toxicology
  • HIV/AIDS Research

Background:

  • Neonatal prophylaxis against Human Immunodeficiency Virus type 1 (HIV-1) is crucial for preventing vertical transmission.
  • Maraviroc, a CCR5 antagonist, has shown efficacy in adults but its use in neonates requires safety and pharmacokinetic evaluation.
  • Standard antiretroviral prophylaxis regimens may be enhanced with novel agents like maraviroc.

Purpose of the Study:

  • To assess the safety and pharmacokinetics of maraviroc in HIV-1 exposed infants.
  • To determine an appropriate maraviroc dosage for neonates during the initial six weeks of life.
  • To evaluate the impact of maternal efavirenz exposure on maraviroc pharmacokinetics.

Main Methods:

  • A Phase I, multicenter, open-label study (IMPAACT 2007) enrolled two sequential cohorts of HIV-exposed neonates.
  • Cohort 1 received two single 8 mg/kg maraviroc doses; Cohort 2 received 8 mg/kg twice daily for six weeks.
  • Pharmacokinetic sampling and clinical/laboratory evaluations were performed to assess safety and exposure targets (Cavg ≥ 75 ng/mL).

Main Results:

  • Fifteen infants in Cohort 1 and 32 in Cohort 2 were enrolled.
  • All evaluable infants in Cohort 1 met the pharmacokinetic target.
  • Median maraviroc exposure in Cohort 2 met the target, though with high variability; 17-33% were below target at weeks 1 and 4.
  • No Grade 3+ toxicities or treatment discontinuations due to maraviroc occurred.
  • Maternal efavirenz exposure did not affect maraviroc pharmacokinetics.

Conclusions:

  • Maraviroc at 8 mg/kg twice daily achieved target exposure in neonates, despite variability.
  • The drug was well-tolerated, with no safety concerns or treatment discontinuations related to maraviroc.
  • Maternal efavirenz use did not impact maraviroc exposure in infants.
  • No HIV-1 infections were observed during follow-up, suggesting potential efficacy of this prophylactic regimen.
Abstract

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