Our mathematical model reveals a threshold condition in which HIV-1 infection is dependent upon the rate that CD4 T cells traffic between compartments (S1 Text). Assuming that the drug sanctuaries are small in size compared to the main compartment, viral replication in the drug sanctuaries is only sustainable when the rate of trafficking of infected CD4 T cells between the drug sanctuaries and the main compartment is below a critical threshold value. Should infected CD4 T cells traffic from the drug sanctuaries into the main compartment faster than the critical threshold rate, the number of secondarily infected cells that arise and remain in the drug sanctuaries would fall below one, and ongoing replication in the sanctuaries would become unsustainable. That is, the basic reproductive number in the drug sanctuaries would be less than one and ongoing replication could not persist in the long-term.