HIV-1 therapy requires combinations of reagents in order to effectively suppress HIV-1 replication. We have created several combinations of anti-HIV reagents through genetic engineering, which will eventually be delivered to humans through adult blood stem cells. We have compared the effectiveness and safety of these genetic “vectors” in cell culture and in an advanced mouse model, which allows human blood cells to grow in tissues. In addition, this mouse model allows one to investigate HIV-1 infection within the animals. Through these tests, we narrowed combinations down to those that seem to be the most effective based upon showing no toxicity and possessing the ability to be maintained within human blood cells in the mouse, and resist multiple strains of HIV-1 infection both in cell culture and in the humanized mice.