While recently widely applied for cancer, the first CAR clinical trials were for HIV-1 infection, testing a CAR composed of the CD4 extracellular domain linked to the intracellular CD3-ζ chain signaling domain (CD4CAR), utilizing CD4 binding to HIV-1 Envelope (Env) for targeting and killing of HIV-1 infected cells by redirected peripheral T cells [9]. Here, CD4 is linked to HIV-1 infection.