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Although nucleos\/tide analogue (NA) therapy is typically highly effective, challenges remain for viral load (VL) suppression, including medication access, incomplete adherence and drug resistance. We present a case of a long-term HBV and HIV coinfected adult prescribed with sequential NA therapy regimens, with episodes of breakthrough viraemia. Multiple factors contribute to virological breakthrough, including exposure to old NA agents, initial high HBV VL, therapy interruptions, intercurrent illnesses and potential contribution from resistance mutations. The case underscores the importance of individualised treatment approaches and adherence support in achieving HBV suppression. Furthermore, it emphasises the need for improved clinical pathways addressing education, support and access to care, particularly for marginalised populations. 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