Nevirapine concentrations in newborns receiving an extended prophylactic regimen

J Acquir Immune Defic Syndr. 2008 Mar 1;47(3):334-7.

Abstract

Background: The optimal neonatal antiretroviral (ARV) regimen for prevention of HIV mother-to-child transmission (MTCT) is unknown for infants born to mothers who receive no ARVs during pregnancy.

Methods: As part of a protocol comparing the efficacy of 3 neonatal ARV regimens in preventing HIV-1 MTCT in neonates born to mothers who receive no prenatal treatment with ARVs, we devised a 3-dose nevirapine (NVP) regimen with the goal of maintaining the NVP plasma concentration >100 ng/mL (10 times the in vitro median inhibitory concentration of 10 ng/mL) during the first 2 weeks of life. NVP concentrations were measured in 14 newborns participating in a pharmacokinetics substudy during the second week of life and in single samples from 30 more newborns on day 10 to 14.

Results: The median NVP elimination half-life was 30.2 hours (range: 17.8 to 50.3 hours). The NVP concentration remained greater than the target of 100 ng/mL in all samples collected through day 10 of life. By day 14, more than half of the newborns in the pharmacokinetic substudy had NVP levels <100 ng/mL, although only 1 neonate had no detectable NVP.

Conclusion: Although this regimen failed to meet our 100-ng/mL target, it did maintain detectable NVP concentrations in nearly all newborns through the end of the second week of life and is to be used in the parent efficacy protocol.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / therapeutic use
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Female
  • HIV Infections / prevention & control*
  • HIV Infections / transmission
  • HIV-1 / drug effects
  • Humans
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Nevirapine / blood
  • Nevirapine / pharmacokinetics
  • Nevirapine / therapeutic use*
  • Pregnancy
  • Pregnancy Complications, Infectious / virology*
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents
  • Nevirapine