Antiretroviral concentrations in breast-feeding infants of mothers receiving highly active antiretroviral therapy.
There are limited data describing the concentrations of zidovudine, lamivudine, and nevirapine in nursing infants as a result of transfer via breast milk. The Kisumu Breastfeeding Study is a phase IIb open-label trial of prenatal, intrapartum, and postpartum maternal treatment with zidovudine, lamivudine, and nevirapine from 34 weeks of gestation to 6 months postpartum. In a pharmacokinetic substudy, maternal plasma, breast milk, and infant dried blood spots were collected for drug assay on the day of delivery and at 2, 6, 14, and 24 weeks after delivery. Sixty-seven mother-infant pairs were enrolled. The median concentrations in breast milk of zidovudine, lamivudine, and nevirapine during the study period were 14 ng/ml, 1,214 ng/ml, and 4,546 ng/ml, respectively. Zidovudine was not detectable in any infant plasma samples obtained after the day of delivery, while the median concentrations in infant plasma samples from postpartum weeks 2, 6, and 14 were 67 ng/ml, 32 ng/ml, and 24 ng/ml for lamivudine and 987 ng/ml, 1,032 ng/ml, and 734 ng/ml for nevirapine, respectively. Therefore, lamivudine and nevirapine, but not zidovudine, are transferred to infants via breast milk in biologically significant concentrations. The extent and effect of infant drug exposure via breast milk must be well understood in order to evaluate the benefits and risks of maternal antiretroviral use during lactation.
Mirochnick
Mark
M
Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA. markm@bu.edu
Thomas
Timothy
T
Capparelli
Edmund
E
Zeh
Clement
C
Holland
Diane
D
Masaba
Rose
R
Odhiambo
Prisca
P
Fowler
Mary Glenn
MG
Weidle
Paul J
PJ
Thigpen
Michael C
MC
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001769:Blood / Q000821:virology; D001942:Breast Feeding; D017322:Clinical Trials, Phase II as Topic; D003890:Desiccation; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D007774:Lactation / Q000378:metabolism*; D019259:Lamivudine / Q000097:blood / Q000493:pharmacokinetics; D019829:Nevirapine / Q000097:blood / Q000493:pharmacokinetics; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine