The present invention is based, at least in part, on the discovery of compositions and methods for the treatment and prevention of infectious diseases or disorders, e.g., HIV infection, AIDS, and AIDS-related diseases. In particular, the present invention pertains to methods of modulating cellular gene expression or protein activity, e.g., CCR5, gene expression or protein activity and/or gene expression or protein activity of a gene or sequence of an infectious agent, in order to treat or prevent infectious diseases or disorders, HIV infection, AIDS, or an AIDS-related disease or disorder. In one embodiment the combination of an RNA interfering agent targeting a cellular gene in combination with an RNA interfering agent targeting a gene or sequence of an infectious agent results in prolonged prevention of infection by an infectious agent. The present invention is based on the identification of novel RNA interference agents, e.g., siRNA molecules, which target cellular genes, e.g., chemokine receptors, e.g., the CCR5 gene, and result in inhibition of target gene expression on target gene expressing cells, thereby inhibiting entry of infectious agents, e,g., HIV infection into target cells, prevention infection, and/or suppressing replication in established infection.