Brief Report: Breast Milk Transfer and Infant Exposures to Dolutegravir, Tenofovir, and Tenofovir Alafenamide: Results From IMPAACT 2010/VESTED.

BACKGROUND

Limited information is available on breast milk transfer and subsequent infant systemic exposure to dolutegravir (DTG), tenofovir alafenamide (TAF), and tenofovir (TFV). We evaluated concentrations of DTG, TAF, and TFV in maternal and infant plasma and breast milk from participants of International Maternal Pediatric Adolescent AIDS Clinical Trials 2010, a clinical trial that enrolled women initiating either a DTG-containing or an efavirenz-containing antiretroviral treatment regimen during pregnancy.

METHODS

Time-matched postpartum maternal and infant samples were collected at 6 weeks postpartum. Validated assays quantitated concentrations of DTG, TAF, and TFV. Relative infant dose was estimated using an average milk intake of 150 mL/kg/d and observed breast milk concentrations.

RESULTS

Data were available from 192 postpartum lactating women and their breastfed infants. Median maternal plasma concentrations of DTG, TAF, and TFV were 2810, 0.0, and 96 ng/mL, respectively. For DTG, median [interquartile range (IQR)] concentrations in breast milk and infant plasma were 91 ng/mL (67-123) and 69 ng/mL (41-95), respectively. TAF was below the quantitative limit (BQL) in nearly all breast milk and infant plasma samples. For TFV, median (IQR) concentrations in breast milk were 8 ng/mL (6-12), and nearly all infant plasma samples were BQL. The median RIDs of DTG, TAF, and TFV from breastfeeding were 1.9%, 0.00%, and 0.03%, respectively.

CONCLUSIONS

Breast milk transfer of DTG, TAF, and TFV is low and results in minimal systemic exposure in breastfed infants. The clinical relevance of infant exposure to low concentrations of these antiretrovirals-particularly DTG-is unknown but should be considered in the context of the risk of drug resistance in infants who acquire HIV.