CD4 and HIV-1 infection: However, cell-based assays used for investigating the effects of modulating SAMHD1 activity on Nt-AI inhibition of HIV-1 infection have demonstrated that the downregulation of SAMHD1 in monocyte-derived macrophages and activated CD4+ T cells results in a large decrease in the efficacy of AZT (14, 29, 30) and, to a lesser extent, in that of other Nt-AIs (29).