In conclusion, the presence of key genetic signature sites in the SP, gp120, V2, glycosite 230, D loop, V3 loop, CD4 contact residues, and LLP-2 in subtype A1 T/Fs, as well as in the C-helix, gp120, V3 loop, and Fusion HR-2 regions of A1D recombinant T/F Envs, may play a crucial role in the successful establishment of acute and the maintenance of long-term infection. Here, CD4 is linked to infection.