Abstract: Chimeric proteins are provided having binding specificity for at least two different sites, at least one site being on the HIV envelope glycoprotein gp120 and the other bite being either on said gp120 protein or on the extracellular portion of human CD4, said chimeric protein comprising: (a) a first binding region comprising a soluble extracellular portion of human CD4; (b) a second binding region comprising a variable region of an antibody heavy chain, preferably VH3; (c) a linker that connects (a) and (b); and, optionally, a portion of a constant region of an immunoglobulin chain. The chimeric proteins are useful for prevention and treatment of HIV infection.