Pharmacokinetic parameters of bictegravir in breastmilk of healthy, lactating volunteers without HIV after a single dose of 50 mg (co‐formulated with emtricitabine 200 mg and tenofovir alafenamide 25 mg)

4 Introduction: The risk of transmission of HIV through breastfeeding is very low when sustained viral suppression is reached using antiretroviral therapy. However, to what extent these antiretroviral drugs transfer in to breastmilk is not fully understood. These data are especially lacking for relatively newer drugs—such as bictegravir—that only recently was approved for use in pregnancy. Therefore, the aim of this study was to determine the infant exposure to bictegravir through breastmilk. Materials and methods: Concentrations of bictegravir were measured in plasma and breastmilk of healthy, lactating women without HIV after a single dose of bictegravir 50 mg (co-formulated with tenofovir alafenamide 25 mg and emtricitabine 200 mg) at predefined timepoints (pre-dose and 1–6, 8, 10, 12 and 24 h after ingestion for plasma and pre-dose and 2, 4, 6, 12 and 24 h after ingestion for breastmilk). The concentrations were measured using validated LC–MS/MS assays, and pharmacokinetic parameters were calculated using non-compartmental analysis (Winnonlin, Phoenix). Breastmilk to maternal plasma ratio, daily infant dosage and relative infant dose were established in order to determine infant exposure to bictegravir through breastmilk. Results: Twelve volunteers participated in the study. The geometric mean (CV%) of the area under the curve was 1.58 (28.8) mg*h/L in plasma and 0.01 (40.5) mg*h/L in breastmilk, resulting in a geometric mean (CV%) breastmilk to maternal plasma ratio of 0.008 (19.4). The median (IQR) daily infant dose (DID) and relative infant dose (RID) of bictegravir in this cohort was 0.008 (0.003–0.012) mg/kg/day and 0.11 (0.05–0.30)% respectively. When extrapolated to infants that are exclusively breastfed with 200 mL/kg/day, the median (IQR) DID is 0.046 (0.035–0.080) mg/kg/day, and the RID is 0.90% (0.71–1.33) in infants receiving up to 150 and 200 mL/kg/day. Conclusion: The exposure to bictegravir through breastmilk is very low, with a relative infant dose below 1%. And even though the metabolizing capacity in newborns is not yet fully developed, it is not expected to cause infant toxicity.