title: Persistence of nevirapine in breast milk and plasma of mothers and their children after single-dose administration.
abstract: OBJECTIVE
  Nevirapine is widely used in the developing world for the prevention of mother-to-child transmission (PMTCT) of HIV. A single mutation in the HIV genome is sufficient to lead to significant nevirapine resistance. Persistence of low-level drug concentrations in body compartments can foster resistance formation. In this study, concentration-time courses of nevirapine after single-dose administration were analysed over an extended post-partum period.
  
  
  METHODS
  Breast milk and plasma samples of 62 HIV-positive Ugandan mother-child pairs who had received single-dose nevirapine were collected at delivery and 1, 2 and 6 weeks post-partum. Nevirapine concentrations were quantified by LC/tandem-mass-spectrometry using a quantification limit of 15 ng/mL, and a population pharmacokinetic (PK) analysis was performed.
  
  
  RESULTS
  Concentration-time profiles in breast milk, maternal plasma and child plasma showed similar shapes. At week 1, median nevirapine concentrations were 164 ng/mL in maternal plasma, 114 ng/mL in breast milk and 183 ng/mL in child plasma. The population PK model predicted nevirapine concentrations>10 ng/mL (IC50 for nevirapine) for 13 days in breast milk, 14 days in maternal plasma and 18 days in child plasma in 80% of the samples.
  
  
  CONCLUSIONS
  Nevirapine concentrations were present for 2-3 weeks in the three compartments. The concentrations are probably sufficiently high to protect most breastfed children from HIV transmission during the first 2 weeks. The long presence of slowly decreasing levels of nevirapine is likely to induce resistance formation. Post-natal addition of antiretrovirals for 1 week only, as recommended in the current PMTCT guidelines, will not suffice to avoid nevirapine resistance formation.
authors.affiliation: Institute of Tropical Medicine and International Health, Charité-University Medicine Berlin, Berlin, Germany. andrea-ursula.kunz@charite.de
authors.forename: Andrea
authors.initials: A
authors.lastname: Kunz
authors.forename: Monika
authors.initials: M
authors.lastname: Frank
authors.forename: Kizito
authors.initials: K
authors.lastname: Mugenyi
authors.forename: Rose
authors.initials: R
authors.lastname: Kabasinguzi
authors.forename: Astrid
authors.initials: A
authors.lastname: Weidenhammer
authors.forename: Michael
authors.initials: M
authors.lastname: Kurowski
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kloft
authors.forename: Gundel
authors.initials: G
authors.lastname: Harms
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid; D005260:Female; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008297:Male; D008895:Milk, Human / Q000737:chemistry*; D009035:Mothers; D019829:Nevirapine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry*; D037841:Pregnant People; D053719:Tandem Mass Spectrometry; D014454:Uganda
chemical_list: D019829:Nevirapine