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Background To increase the immunosurveillance in HIV infection, we used retroviral vectors expressing CD4-chimeric antigen receptors ( CARs) to genetically modify autologous T cells and redirect CTL toward HIV. The CD4 extracellular domain targets envelope and the intracellular signaling domains activate T cells. The maC46 fusion inhibitor binds HIV and blocks viral replication. Methods We stimulated rhesus PBMCs with antibodies to CD3/CD28 and cotransduced T cells with CD4- CAR and maC46 vectors. CD4- CAR-transduced T cells were added to Env+ 293T cells at E:T of 1:1. Killing of target cells was measured as reduced impedance. Results We observed gene expression in 60-70% of rhesus CD3+ CD8+ T cells with the individual vectors and in 35% of the cells with both vectors. CD4- CAR-transduced populations specifically killed Env+ cells. Conclusions In these studies, we showed that designer T cells were redirected to kill Env+ cells. Control of viremia without HAART would revolutionize treatment for HIV patients. [ABSTRACT FROM AUTHOR]