Even within a particular tissue, cells may respond differently to trafficking signals owing to the expression of distinct homing receptors and their differentiation status and activation state [40–42]. Whereas effector memory and central memory T cells recirculate between blood, lymphoid tissue, and lymph, resident memory T cells do not circulate through the blood . Thus, functional changes are associated with T cell migration. Although the existence of some cell types within a drug sanctuary that are unresponsive or less responsive to trafficking signals does not preclude an effective outcome of trafficking therapy, it does make it more difficult. The outcome of trafficking therapy would depend upon the fraction of cells of each type, the degree to which each of their trafficking patterns can be manipulated and the degree to which these different cell types mix together. Ultimately, if different cells types within a sanctuary mix homogeneously, and if the average residency time of infected cells in a drug sanctuary (across all cell types) can be sufficiently reduced, replication can still be rendered unsustainable.