In demonstrating that ongoing cycles of replication in drug sanctuaries require CD4 T cell trafficking between compartments to be below a critical threshold, our model suggests a novel approach to HIV-1 control. It predicts that therapy designed to increase the trafficking of CD4 T cells into and out of drug sanctuaries above a threshold rate could halt ongoing cycles of replication. Although a ‘trafficking therapy’ of this sort would affect infected and uninfected cells equally, the mechanism through which it would work is by decreasing the mean residence time of infected cells in drug sanctuaries, moving them into the main compartment where drug concentrations are sufficient to block new rounds of infection with HIV-1 (Fig 3).