Background:  The Breastfeeding, Antiretroviral, and Nutrition (BAN) study is enrolling >2400 pregnant women in Malawi to evaluate the effect on prevention of mother-to-child transmission (PMTCT) of:  28 weeks of HAART given to mothers or daily nevirapine (NVP) given to babies; weaning at 28 weeks; and nutritional supplementation. All mothers and infants receive single-dose NVP and 7 days' zidovudine (ZDV)/lamivudine (3TC) peripartum. Entry criteria include maternal CD4 >200 cells/µL and infant birth weight >2kg. To better understand infant drug exposure from breast milk, a longitudinal pharmacokinetic study in mother–infant pairs was performed.

Methods:  Breast milk, and mothers' and infants' blood plasma were obtained at the end of 12-hour dosing intervals at 6, 12, and 24 weeks post partum. Based on tolerability, mothers' regimens included a combination of ZDV (or stavudine [d4T]), 3TC, and either NVP or nelfinavir (NFV). Drug concentrations were measured using validated high-performance liquid chromatography (HPLC)/mass spectrometry (MS)/MS methods. Demographic and concentration data are presented as median (range) and median (IQR), respectively.  

Results:  We enrolled 20 mother–infant pairs. Mothers were 26 (19 to 35) years old and weighed 53 (46 to 54) kg with CD4 counts 518 (216 to 931) cells/µL at delivery. Babies weighed 3.1 (2.2 to 2.6) kg at delivery, and 75% were male. Samples were obtained at a median of 15, 12, and 17 hours post-dose at 6, 12, and 24 weeks post partum (in the table below n = number of samples). Predictably, <20% of samples had detectable ZDV and d4T. Maternal plasma concentrations for other antiretrovirals were similar to previous reports. 3TC, NVP, and NFV concentration ratios are represented below with all time points included. 3TC and NVP infant's plasma concentrations declined slightly from 6 to 24 weeks post-partum, while mothers' plasma and breast milk concentrations did not significantly change.

Conclusions:  Although 3TC concentrations in breast milk were 2.6-fold higher than in maternal plasma, infant plasma exposure was minimal (1% of breast milk). NVP concentrations in breast milk were ~70% that of maternal plasma, with low exposure (20% of breast milk) in infants. NFV exposure in breast milk is minimal (8% of maternal plasma), with no drug found in infants. Infants' plasma concentrations for all antiretrovirals were well below concentrations required for treatment, suggesting minimal risk for drug toxicity. 3TC and NFV exposure in infants would suggest minimal risk for resistance in HIV-infected children; however, low-level NVP exposure via breast milk may predispose HIV-infected infants to resistance.