Transfer of antiretroviral drugs into breastmilk: a prospective study from the Swiss Mother and Child HIV Cohort Study

Abstract

Introduction In 2018, Switzerland changed its guidelines to support women living with HIV wishing to breastfeed. The exposure of antiretroviral drugs (ARVs) in breastmilk and the ingested daily dose by the breastfed infant are understudied, notably for newer ARVs. This study aimed to quantify ARV concentrations in maternal plasma and breastmilk to determine the milk/plasma ratio, to estimate daily infant ARV dose from breastfeeding and to measure ARV concentrations in infants. Methods All women wishing to breastfeed were included, regardless of their ARV treatment. Breastmilk and maternal plasma samples were mostly collected at mid-dosing interval. Results Twenty-one mother/child pairs were enrolled; of those several were on newer ARVs including 10 raltegravir, 1 bictegravir, 2 rilpivirine, 2 darunavir/ritonavir and 3 tenofovir alafenamide. No vertical HIV transmission was detected (one infant still breastfed). The median milk/plasma ratios were 0.96/0.39 for raltegravir once/twice daily, 0.01 for bictegravir, 1.08 for rilpivirine, 0.12 for darunavir/ritonavir and 4.09 for tenofovir alafenamide. The median estimated infant daily dose (mg/kg) from breastfeeding was 0.02/0.25 for raltegravir once/twice daily, 0.01 for bictegravir, 0.02 for rilpivirine, 0.05 for darunavir/ritonavir and 0.007 for tenofovir alafenamide, resulting in relative infant dose <10% exposure index for all ARVs. Conclusions ARVs were transferred to a variable extent in breastmilk. Nevertheless, the estimated daily ARV dose from breastfeeding remained low. Differential ARV exposure was observed in breastfed infants with some ARVs being below/above their effective concentrations raising the concern of resistance development if HIV infection occurs. More data on this potential risk are warranted to better support breastfeeding.

A systematic review on maternal-to-infant transfer of drugs through breast milk during the treatment of malaria, tuberculosis, and neglected tropical diseases

“…A wide intra- and interstudy variability due to differences in pharmacokinetic sampling times, drug concentration assays, statistical methods used for data analysis, and biological differences between populations were reported, all that affect the interpretation of observed findings [ 59 ]. A more recent study characterized the breast milk transfer of the relatively newer antiretroviral drugs including dolutegravir, raltegravir, bictegravir, rilpivirine, and darunavir, showing high rilpivirine transfer, moderate to high transfer of raltegravir, and low transfer of bictegravir and dolutegravir [ 60 ]. Bictegravir and dolutegravir showed high infant concentrations despite the low breast milk concentrations observed [ 60 ], which, in the case of dolutegravir, relates to the high transplacental transfer of drug (cord: maternal blood ration of 1.2) and prolonged infant clearance due to immaturity of UGT1A1 [ 61 ].…”

Infant feeding: emerging concepts to prevent HIV transmission

“…Agents were detectable in infant plasma, below the exposure index of 10% (safety threshold for infant exposure to maternal drugs through breastmilk). Infant plasma concentrations did not necessarily correlate with those in breastmilk [ 14 ▪ ].…”