The invention is directed to polypeptides comprising a CD4 binding moiety, a gp41 binding moiety, a HIV fusion peptide inhibitor moiety and combinations thereof. More specifically, the present invention relates to polypeptides comprising a fibronectin-based scaffold domain protein that binds CD4, a fibronectin-based scaffold domain protein that binds the N17 domain of gp41, and a HIV fusion peptide inhibitor or combinations thereof. The invention also relates to the use of the innovative proteins in therapeutic applications to treat HIV.