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. 2009 Mar;53(3):1170-6.
doi: 10.1128/AAC.01117-08. Epub 2008 Dec 29.

Antiretroviral concentrations in breast-feeding infants of mothers receiving highly active antiretroviral therapy

Mark Mirochnick  1 , Timothy Thomas, Edmund Capparelli, Clement Zeh, Diane Holland, Rose Masaba, Prisca Odhiambo, Mary Glenn Fowler, Paul J Weidle, Michael C Thigpen
Affiliations

Antiretroviral concentrations in breast-feeding infants of mothers receiving highly active antiretroviral therapy

Mark Mirochnick et al. Antimicrob Agents Chemother. 2009 Mar.

Abstract

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.

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Figures

FIG. 1.
FIG. 1.
Infant concentrations (conc) of zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) on day of delivery (DEL) and at 2, 6, 14, and 24 weeks postpartum, Kisumu Breastfeeding Study, Kenya, 2004 to 2007. For comparative purposes, the IC50 for wild-type HIV type 1, subtype B, is ∼0.6 to 21 ng/ml for lamivudine and ∼17 ng/ml for nevirapine.
FIG. 2.
FIG. 2.
Maternal plasma and breast milk concentrations (conc) of zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) plotted against time since last maternal dose, Kisumu Breastfeeding Study, Kenya, 2004 to 2007. Dashed lines are regression lines for maternal plasma data, and solid lines are regression lines for breast milk data.
FIG. 3.
FIG. 3.
Zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) breast milk (BM)-to-maternal plasma ratio plotted against time since last maternal dose, Kisumu Breastfeeding Study, 2004 to 2007. The filled circles represent samples with zidovudine breast milk concentrations below the limit of detection and represent the highest possible breast milk/plasma ratio. The P values represent the probability that the slope of the line is different than zero as calculated by linear mixed-effects regression analysis.
FIG. 4.
FIG. 4.
Proportion of breast-feeding infants receiving a cumulative breast milk nevirapine dose of 2 mg/kg plotted against number of days of breast feeding (estimated from day-of-delivery breast milk nevirapine concentrations), Kisumu Breastfeeding Study, Kenya, 2004 to 2007.
FIG. 5.
FIG. 5.
Observed and model-predicted infant dried blood spot (DBS) nevirapine (NVP) concentrations (conc) at weeks 2, 6, and 14 postpartum, Kisumu Breastfeeding Study, Kenya, 2004 to 2007.
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