The present invention describes a method to inhibit replication of the human immunodeficiency virus (HIV) by negatively modulating or altering the cytoskeleton, more precisely the proteins forming the intermediate cytoskeletal filaments, wherein the said proteins are vimentin and/or keratin-la The replication of the virus is inhibited in human cells by intervening in the structure of these proteins. The present invention is also related to the use of agents, which comprise peptides and/or interfering RNA and/or lipidic compounds, said agents producing a negative modulation or alteration of the cytoskeleton to prevent or to treat the HIV infection. The invention provides means and methods for altering the cytoskeleton/filament structure of cells, as a result of which the infection of human cells by HIV is disturbed and can even be completely inhibited. The cytoskeleton is altered by reducing the amount of vimentin and/or keratin (e.g. by transcriptional control using interfering RNA) or by using peptides that disrupt the cytoskeleton.