Two series of water-soluble dendritic catanionic assemblies, acting as multisite analogues of galactosylceramide (Galbeta1cer), have been prepared with the goal of blocking HIV infection prior to the entry of the virus into human cells. Trifunctional and hexafunctional cinnamic acid-terminated dendrimers have been synthesized from phosphorus-containing dendrimers bearing aldehyde end groups. A classical acid-base reaction performed in water between acid-terminated dendrimers and stoichiometric amounts of N-hexadecylamino-1-deoxylactitol provided the expected catanionic assemblies. Antiviral assays on these supramolecular entities confirmed the crucial roles both of multivalency effects and of lipophilicity on the biological activity of Galbeta1cer analogues. Moreover, correlation between in vitro tests and molecular modeling highlights the specific influence of the assembly shape on the anti-HIV efficiency, with the tri- and hexafunctional cored dendrimers, both decorated with 12 sugar moieties, exhibiting IC50 values of 1.1 and 0.12 microM, respectively.