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Introduction: We sought to understand the Undetectable = Untransmittable (U = U) communication needs of persons living with HIV (PLHIV) and barriers to U = U communication among healthcare providers (HCPs) in South Africa. Methods: We conducted five focus group discussions (FGDs) with HCPs (N = 42) including nurses and counsellors from primary healthcare clinics (PHCs) in the Gauteng and Free State Provinces of South Africa, three FGDs (N = 27) with PLHIV recruited by snowball sampling from civil society organizations, and 27 in-depth interviews (IDIs) with recently diagnosed PLHIV in Johannesburg. IDIs and FGDs were audio recorded, transcribed, translated to English, and analysed thematically. Results: PLHIV were largely unaware and sceptical of U = U as the message appeared to contradict the mainstream HIV prevention clinical guidance. The low viral load (VL) knowledge further reduced confidence in U = U. PLHIV need support and guidance on the best approaches for sharing U = U information and disclosing their VL status to their partners, highlighting the central role of community understanding of U = U and VL to mediate the desired stigma reduction, social acceptance and emotional benefits of U = U for PLHIV. HCPs were uneasy about sharing U = U due to concerns about risk compensation and ART non-adherence and worried about enabling any ensuing HIV transmission. HCPs also need a simple, unambiguous, and consistent narrative for U = U, integrated with other HIV prevention messages. PLHIV and HCPs alike recommended a patient-centred approach to communicating U = U, focusing primarily on attaining viral suppression and emphasizing that condomless sex is only safe during periods of ART adherence. Conclusions: These data highlight the need for simple U = U communication support targeting both HCP and PLHIV. Culturally appropriate communication materials, with training and ongoing mentorship of the clinic staff, are essential to improve patient-centred U = U communication in clinics. [ABSTRACT FROM AUTHOR]