# Bictegravir concentrations in breastmilk of healthy, lactating women without HIV

## TL;DR

This study measures how much of the HIV drug bictegravir passes into breastmilk and finds that infant exposure is very low.

## Contribution

The study provides first-time data on bictegravir concentrations in breastmilk of HIV-negative lactating women.

## Key findings

- Bictegravir breastmilk concentrations were much lower than plasma concentrations.
- Infant doses from breastmilk were below 1% of maternal doses and unlikely to cause toxicity.
- Pharmacokinetic parameters showed minimal transfer of bictegravir into breastmilk.

## Abstract

Risk of transmission of HIV through breastfeeding is minimal in case of maternal viral suppression due to antiretroviral therapy. However, to what extent antiretroviral drugs transfer into breastmilk is not fully understood. Data are especially lacking for relatively newer drugs—such as bictegravir—that only recently was approved to use in pregnancy. Therefore, the aim of this study is to determine infant exposure to bictegravir through breastmilk.

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). Concentrations were measured using validated LC-MS/MS assays and pharmacokinetic parameters were calculated using non-compartmental analysis. Breastmilk to maternal plasma ratio, daily infant dosage and relative infant dose were established to determine infant exposure to bictegravir through breastmilk.

Twelve volunteers participated in the study. The geometric mean (CV%) area under the curve based on the last measured concentration was 52.17 (22.6) mg*h/L in plasma and 0.44 (32.0) mg*h/L in breastmilk, resulting in a geometric mean (CV%) breastmilk to maternal plasma ratio of 0.009 (26.6). The median (IQR) daily infant and relative infant doses with an intake of 150 or 200 mL/kg/day were 0.034 mg/kg/day (0.026–0.060) and 0.046 (0.035–0.080) mg/kg/day and 0.68 (0.53–1.00) % and 0.90% (0.71–1.33), respectively.

Exposure to bictegravir through breastmilk is very low, with a relative infant dose below 1%. Even though metabolizing capacity in newborns is not yet fully developed, it is not expected to cause infant toxicity.