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Novel approaches aimed at eliminating these reservoirs are therefore essential for an HIV-1 cure. Among emerging cure strategies, harnessing antibody-dependent cellular cytotoxicity (ADCC) has generated significant interest. In this mGem, we discuss how small CD4-mimetic compounds (CD4mc), by forcing envelope (Env) into more \u201copen\u201d conformations, thereby exposing conserved CD4-induced epitopes, can unlock the ADCC potential of non-neutralizing antibodies. We also highlight how type I interferons complement this approach by upregulating BST-2, thereby increasing Env at the cell surface, diminishing Vpu-mediated immune evasion, and enhancing NK cell effector functions. 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