Here, we extend these studies by developing a D13 duoCAR LV optimized for clinical translation, and we demonstrate its ability to generate anti-HIV duoCAR T cells that display potent in vitro killing of HIV-infected monocytes and CD4+ T cells and the in vivo capacity — after i.v. injection — to migrate to the active site of HIV infection in the spleens of humanized mice and potently suppress HIV infection. The gene discussed is CD4; the disease is HIV infectious disease.