Given our data and observations from studies described above, we surmise that selective pressures during in utero transmission yield infant isolates with low CD4 requirements for productive infection, and that are well-poised to infect placental macrophages (e.g., Hofbauer cells) that have lower cell surface CD4 densities, perhaps through exploiting higher CD4 avidity, direct co-receptor binding, and/or having enhanced fusogenic properties. Here, CD4 is linked to infection.