Molecular genetic intervention in the replication cycle of the human immunodeficiency virus type 1 (HIV-1) is currently thought to be a viable treatment for AIDS. Because replication of the virus is strictly dependent upon the function of two essential viral regulatory proteins, tat and rev, they are excellent targets for novel approaches for therapeutic intervention in HIV-1-infected individuals. Using retroviral vectors to genetically modify CD4+ T-cell lines, it has been shown that certain cell types susceptible to HIV/simian immunodeficiency virus (SIV) infection and replication can be made to resist virus replication. Using the SIV/rhesus macaque system as a model, the potential use of gene therapy approaches to combat HIV infections in humans will be further evaluated. Approaches currently ongoing include developing methods and techniques to increase the efficiency of retroviral-mediated transduction of rhesus macaque hematopoietic stem cells.