Pharmacokinetics and safety of maraviroc in neonates.

Objective To evaluate safety and pharmacokinetics (PK) 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 Phase I, multi-center, 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 one week apart with PK sampling after each dose. Cohort 2 participants received 8 mg/kg maraviroc twice daily through 6 weeks of life with PK sampling at weeks 1 and 4. Maraviroc exposure target was Cavg ≥ 75ng/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 PK target. Median exposure for the 25 evaluable Cohort 2 infants met the PK target but variability was high, with 17-33% of infants below target at Weeks 1 and 4. PK target achievement was similar between efavirenz exposure strata. No Grade 3+ toxicities, early study, or treatment discontinuations due to maraviroc occurred. Conclusions 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 safe and well-tolerated during the first 6 weeks of life.