by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer

December 6, 2022

Featured Literature:
Aebi-Popp K, Kahlert CR, Crisinel PE, et al.  Transfer of antiretroviral drugs into breastmilk: a prospective study from the Swiss Mother and Child HIV Cohort Study.  J Antimicrob Chemother.  2022 Nov 28; 77(12): 3436-3442.  doi:10.1093/jac/dkac337.  PMID 36177836.  

This study describes ARV concentrations in the breastmilk and maternal plasma of 21 Swiss mothers on HIV treatment (2019-2021), to estimate daily infant ARV dose from breastfeeding.  Infant plasma ARV concentrations were also measured.  All mothers had viral load < 50 copies/mL (ideally throughout pregnancy) and routine clinical evaluation occurred via monthly visits per Swiss care guidelines.  No infants received post-exposure prophylaxis, as per Swiss recommendations.  Maternal breastmilk and plasma samples were obtained at 1-, 3-, and 6-month follow-up visits after delivery.  Infants were tested at 1 and 6 months of age by PCR and again 3 months after weaning; serologic testing was performed at 18-24 months of age.  Most mothers were receiving INSTI-based treatment (1 bictegravir, 3 dolutegravir, 10 raltegravir), 2 were on rilpivirine-based combinations, and 2 were on ritonavir-boosted darunavir.  Three were receiving tenofovir alafenamide (TAF).  No HIV transmissions were identified.  Sample analyses demonstrated rilpivirine and tenofovir [derived from TAF] transfer well in breastmilk (similar to other NNRTIs and most NRTIs).  By contrast, darunavir/ritonavir (like other PIs) has low transfer.  INSTI transfer was variable: bictegravir and dolutegravir have low transfer, and raltegravir has moderate-high transfer.  Very low or undetectable levels for rilpivirine, raltegravir, darunavir/ritonavir, and tenofovir [derived from TAF] were observed in infants.  Efavirenz, nevirapine, and dolutegravir were detectable in infants.  Overall, the estimated daily infant ARV dose from breastfeeding was low for all evaluated ARVs and fell within the safety threshold (exposure index < 10%).

Author’s Commentary:

Information from this investigation may help address questions regarding the breastfeeding-associated safety of various ARVs when taken as part of maternal HIV treatment.  Unsurprisingly, study data demonstrate that ARVs transfer into breastmilk and in breastfed infants to different extents: results for DRV/RTV and RPV generally followed historical observations in the PI and NNRTI classes, respectively.  By contrast, transfer differed between specific INSTIs.  Not all studied ARVs achieved effective inhibitory concentrations in the breastfed infant, and therefore one caution noted by authors is that the clinical relevance of subtherapeutic ARV concentrations in breastmilk (as well as differential drug exposure in infants) is unknown.  Both may lead to concerns related to “potential development of resistance in the rare event of vertical transmission” as well as “monotherapy exposure and related risk of acquiring resistant HIV strains”.  It is also noteworthy, however, that no postnatal transmissions were identified among breastfed infants, none of whom received any post-exposure prophylaxis. 

The author has no conflicts of interest to disclose.

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