Efavirenz and Lopinavir Levels in HIV-Infected Women and Their Nursing Infants, in Mali

J Pharmacol Exp Ther. 2018 Sep;366(3):479-484. doi: 10.1124/jpet.118.249938. Epub 2018 Jul 9.

Abstract

Limited data are currently available on antiretroviral pharmacokinetics in breast milk (BM) and in breastfed infants' blood. To explore these parameters in patients in Mali, we measured plasma antiretroviral levels in human immunodeficiency virus (HIV)-infected mothers and their breastfed infants over 6 months. We specifically analyzed the concentrations of efavirenz (EFV) and lopinavir (LPV) in the plasma of mothers living with HIV and their breastfed infants. Blood samples were collected at delivery and at month 1, 3, and 6 postpartum. EFV and LPV concentrations were measured by liquid chromatography-tandem mass spectrometry. HIV-1 RNA load was measured by Abbott M2000RT RealTime System at delivery and 6 months postpartum for mothers, and at 3 and 6 months postbirth for infants. The median duration of antiretroviral therapy at study inclusion was 57 months [interquartile range (IQR), 0-168 months]. The median EFV ratios of infant plasma/maternal plasma (MP) were 0.057 at month 1, 0.072 at month 3, and 0.048 at month 6. During the study period, the median BM/MP ratio of EFV was 1.16 (IQR, 0.96-20.62), which corresponds to a relative infant dose of 2.46% of the recommended weight-adjusted pediatric EFV dose at month 6. The apparent infant clearance of EFV was 0.146 l/h per kilogram at month 6. The LPV concentrations in the plasma of all infants were undetectable. No drug-related adverse reaction or toxicity was observed in any of the infants. The two women who presented a viral load of >50 copies/ml at month 6 had undetectable plasma drug concentrations at the same period. This study showed that breastfed infants received a low level of EFV but not LPV from their treated mothers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alkynes
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / blood*
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / therapeutic use
  • Benzoxazines / adverse effects
  • Benzoxazines / blood*
  • Benzoxazines / pharmacokinetics
  • Benzoxazines / therapeutic use
  • Breast Feeding*
  • Cyclopropanes
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Infant
  • Lopinavir / adverse effects
  • Lopinavir / blood*
  • Lopinavir / pharmacokinetics
  • Lopinavir / therapeutic use
  • Male
  • Mali
  • Mothers*
  • Safety
  • Tissue Distribution
  • Young Adult

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Lopinavir
  • efavirenz