title: Hair and plasma data show that lopinavir, ritonavir, and efavirenz all transfer from mother to infant in utero, but only efavirenz transfers via breastfeeding.
abstract: BACKGROUND
  As efforts intensify to eliminate perinatal HIV transmission, understanding kinetics of maternal-to-child transfer of antiretrovirals during pregnancy and breastfeeding is critical. Antiretroviral levels in plasma, cord blood, and breastmilk reflect exposure over short intervals. Hair concentrations reflect cumulative exposure and can uniquely quantify in utero transfer of maternal medications to infants. We measured plasma and hair antiretroviral levels in HIV-infected Ugandan mothers and their infants at delivery and during breastfeeding to assess transfer.
  
  
  METHODS
  HIV-infected pregnant women were randomized to lopinavir/ritonavir- or efavirenz-based therapy in a larger trial (the Prevention of Malaria and HIV disease in Tororo, PROMOTE). At 0, 8, and 12 weeks postpartum, plasma antiretroviral levels were measured in 117 mother-infant pairs; hair levels were assayed at 12 weeks. Ratios and correlations of infant:maternal concentrations were calculated.
  
  
  RESULTS
  By 12 weeks, 90.4% of mothers reported exclusive breastfeeding. Hair and plasma levels over time suggest moderate (47%) to extensive (87%) in utero transfer of lopinavir and ritonavir, respectively, but negligible transfer of either via breastfeeding. Moderate transfer of efavirenz occurs during pregnancy and breastfeeding (40% cumulative; 15% during breastfeeding). Despite differences in exposure, no infant seroconversions or correlations between infant hair/plasma antiretroviral levels and adverse effects were observed.
  
  
  CONCLUSIONS
  Using a unique approach combining hair and plasma data, we found that different antiretrovirals have distinct kinetics of mother-to-infant transfer. Efavirenz transfers during both pregnancy and breastfeeding, whereas lopinavir and ritonavir transfer only in utero. Further study of the degree and timing of maternal-to-child transfer by antiretroviral will help optimize strategies that protect infants and minimize toxicities during periods of risk.
authors.affiliation: *Department of Medicine, University of California, San Francisco, San Francisco, CA; †Infectious Diseases Research Collaboration, Makerere University College of Health Sciences-University of California, San Francisco, Kampala, Uganda; Department of ‡Clinical Pharmacy; §Center for AIDS Prevention Studies; ‖Departments of Pediatrics; ¶Bioengineering and Therapeutic Sciences; and #Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA.
authors.forename: Monica
authors.initials: M
authors.lastname: Gandhi
authors.forename: Julia
authors.initials: J
authors.lastname: Mwesigwa
authors.forename: Francesca
authors.initials: F
authors.lastname: Aweeka
authors.forename: Albert
authors.initials: A
authors.lastname: Plenty
authors.forename: Edwin
authors.initials: E
authors.lastname: Charlebois
authors.forename: Theodore D
authors.initials: TD
authors.lastname: Ruel
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Tamara
authors.initials: T
authors.lastname: Clark
authors.forename: Veronica
authors.initials: V
authors.lastname: Ades
authors.forename: Paul
authors.initials: P
authors.lastname: Natureeba
authors.forename: Flavia A
authors.initials: FA
authors.lastname: Luwedde
authors.forename: Jane
authors.initials: J
authors.lastname: Achan
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
authors.forename: Deborah
authors.initials: D
authors.lastname: Cohan
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006197:Hair / Q000737:chemistry*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D061466:Lopinavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008895:Milk, Human / Q000737:chemistry*; D010949:Plasma / Q000737:chemistry*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014454:Uganda
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D061466:Lopinavir; C098320:efavirenz; D019438:Ritonavir