We are working on a cure for HIV using blood stem cell transplantation of HIV-infected individuals. We have completed the development of a second generation of anti-HIV genes with potent anti-viral activity and reduced toxicity from our first generation products. We have demonstrated that we can modify adult human blood stem cells with these vectors and that macrophage and T-cell progeny of these modified cells are resistant to HIV infection and spread. We are currently screening the genes to identify the next drug development candidate using a humanized mouse model developed in our laboratory. The completion of these experiments will allow us to immediately move towards clinical testing. This approach to HIV therapy is likley to replace drug therapy and may result in a functional or sterilizing cure for HIV.