Breastfeeding on ART and a closer look at drug transfer to HIV-exposed uninfected infants.

Adherence to antiretroviral therapy (ART) and maintaining an undetectable maternal HIV viral load effectively prevent intrauterine and perinatal HIV transmission 1, 2. However, concerns remain regarding the safety of breastfeeding in infants exposed to maternal ART. This retrospective study analyzed eight breastfed HIV-exposed uninfected (HEU) infants who were followed from January 2015 to July 2022. Maternal ART regimens included abacavir/lamivudine (n = 2), tenofovir alafenamide/emtricitabine (n = 1) or tenofovirdisoproxil/emtricitabine (n = 5) in combinations with rilpivirine (n = 3) (RPV), dolutegravir (n = 2) (DTG), raltegravir (n = 1), darunavir/ritonavir (n = 1), or nevirapine (n = 1). Infants and mothers underwent sequential HIV-PCR testing, complete blood count, and ART drug monitoring in breast milk, infant serum, and maternal serum when available. The relative infant dose (RID) was calculated to assess drug exposure. Hematological parameters were compared with those of 62 HEU formula-fed infants from the same institution. No HIV transmission occurred. ART serum levels in breastfed infants varied significantly, with RPV and DTG levels above the adult target range in two cases. Notably, one infant had RPV levels exceeding the target RID by 633%, leading to cessation of breastfeeding. At four months, mean absolute neutrophil counts were lower in breastfed infants (1,130/µl) compared to formula-fed infants (2,000/µl), with the lowest individual absolute neutrophil counts in the formula-fed group. Despite ART levels above the adult target range in 3 infants, there was no consistent pattern between neutropenia and elevated ART levels. Our findings highlight the substantial variability in infant ART exposure during breastfeeding. Given this variability and the potential for drug accumulation in individual cases, maternal therapeutic drug monitoring should be considered to identify elevated levels early on. In such situations, infant monitoring tailored to the individual may also be warranted.