The hectic clonal expansion of memory CD4 T-cells in HIV infection is a double-edged sword in both AIDS pathology and cure, which not only allows cells to be killed by HIV but also allows cells to die evil via pyroptosis, in sharp contrast to the programmed cell death of immune replenishment via apoptosis (Figure 1) [10, 23, 41–43, 73–79]. Here, CD4 is linked to AIDS.