Does U=U apply during breastfeeding? An urgent research priority.

Whether undetectable equals untransmittable (U=U) applies during breastfeeding remains one of the most consequential unanswered questions in HIV prevention. Although sustained viral suppression eliminates sexual HIV transmission, evidence is insufficient to determine whether breastfeeding transmission risk reflects biological limits of U=U or failure to maintain viral suppression postpartum. Existing data suggest exceedingly low breastfeeding transmission risk with maternal viral suppression, but are limited by infrequent viral load monitoring, older antiretroviral therapy regimens, incomplete follow-up, and sparse breastmilk virology data. This uncertainty has important implications for women with HIV, clinicians, and policy makers, particularly in settings with high burden of HIV where breastfeeding is essential for infant health, survival, neurodevelopment, and nutrition, as well as maternal health. Rigorous prospective studies are urgently needed to answer the question of whether U=U applies during breastfeeding, using modern integrase inhibitor-based antiretroviral therapy, frequent plasma and breastmilk viral load testing, infant follow-up, and rights-based counselling frameworks. Regardless of whether future evidence demonstrates zero or very low residual risk, we strongly argue that women with HIV should be supported to make informed choices regarding infant feeding, grounded in autonomy, evidence, and shared decision making.