As expected, the inhibitory effect of ETO on HIV infection was lost after siRNA‐mediated SAMHD1 depletion (SAMHD1 KD) (Fig 2A) or treatment of MDM with SIVmac virus‐like particles containing Vpx/Vpr (SIV VLP; Figs 2B and EV2), which was confirmed by a dose titration of HIV‐1 virus on SAMHD1 KD (Fig EV3A) and SIV VLP‐treated cells (Fig EV3B) and by infecting control and SAMHD1 KD cells at MOI achieving equal percentage of infected cells (Fig EV3C and D). This evidence concerns the gene SAMHD1 and HIV infectious disease.