title: Concentrations of tenofovir, lamivudine and efavirenz in mothers and children enrolled under the Option B-Plus approach in Malawi.
abstract: OBJECTIVE
  To evaluate antiretroviral drug concentrations in mothers and infants enrolled under the Option B-Plus approach for the prevention of HIV mother-to-child transmission in Malawi and to assess the maternal virological response after 1 year of treatment.
  
  
  METHODS
  Forty-seven women and 25 children were studied. Mothers were administered during pregnancy a combination of tenofovir, lamivudine and efavirenz and continued it during breastfeeding (up to 2 years) and thereafter. Drug concentrations were evaluated in mothers (plasma and breast milk) at 1 and 12 months post-partum and in infants (plasma) at 6 and 12 months of age. Drug concentrations were determined using an LC-MS/MS validated methodology.
  
  
  RESULTS
  In breast milk, tenofovir concentrations were very low (breast milk/maternal plasma ratio = 0.08), while lamivudine was concentrated (breast milk/plasma ratio = 3) and efavirenz levels were 80% of those found in plasma. In infants, median levels at 6 months were 24 ng/mL tenofovir, 2.5 ng/mL lamivudine and 86.4 ng/mL efavirenz. At month 12, median levels were below the limit of quantification for the three drugs. No correlation was found between drug concentrations and laboratory parameters or indices of growth. HIV-RNA >1000 copies/mL was seen at month 1 in 15% of the women and at month 12 in 8.5%. Resistance was found in half of the women with detectable viral load.
  
  
  CONCLUSIONS
  Breastfeeding infants under Option B-Plus are exposed to low concentrations of antiretroviral drugs. With this strategy, mothers had a good virological response 1 year after delivery.
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Palombi
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Pirillo
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Marchei
authors.affiliation: DREAM Program, Community of S. Egidio, PO Box 30355, Blantyre, Malawi.
authors.forename: Haswell
authors.initials: H
authors.lastname: Jere
authors.affiliation: DREAM Program, Community of S. Egidio, PO Box 30355, Blantyre, Malawi.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Sagno
authors.affiliation: DREAM Program, Community of S. Egidio, PO Box 30355, Blantyre, Malawi.
authors.forename: Richard
authors.initials: R
authors.lastname: Luhanga
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Floridia
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Andreotti
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Clementina Maria
authors.initials: CM
authors.lastname: Galluzzo
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pichini
authors.affiliation: Diagnostics Department, Ministry of Health, PO Box 30377, Lilongwe 3, Malawi.
authors.forename: Ruben
authors.initials: R
authors.lastname: Mwenda
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Mancinelli
authors.affiliation: LUMSA University, Via Transpontina 21, 00193 Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Marazzi
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Liotta
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy marina.giuliano@iss.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Giuliano
mesh_terms: D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000493:pharmacokinetics*; D018791:CD4 Lymphocyte Count; D002853:Chromatography, Liquid; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000635:transmission*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019259:Lamivudine / Q000493:pharmacokinetics*; D008295:Malawi; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D053719:Tandem Mass Spectrometry; D000068698:Tenofovir / Q000493:pharmacokinetics*; D019562:Viral Load; D055815:Young Adult
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D019259:Lamivudine; D000068698:Tenofovir; C098320:efavirenz