A new series of bis-functionalized fullerene C(60) derivatives bearing two or more solubilizing chains have been evaluated for their activity against HIV-1 and HIV-2 strains. Some of the compounds show activity against HIV-1 type in the low micromolar range. The effect of the positions of the addends on the C(60) nucleus has been investigated, indicating that only trans-2 isomers possess promising activity. The presence of a quaternary pyrrolidinium nitrogen is essential to increase solubility.