Here we have demonstrated the theoretical potential of using trafficking therapy to stop ongoing replication in drug sanctuaries. There are several practical challenges to the development of safe and effective drugs that can achieve this, however. While this strategy is not restricted to any particular tissue that might harbour a sanctuary, no single therapeutic agent would be expected to usefully impact trafficking to all drug sanctuary sites. By regulating a receptor required for trafficking into one particular tissue, CD4 T-cells could be redistributed to another tissue, where drug sanctuaries also exist. As we have demonstrated (see Eq 5), this could increase the effective reproductive number in these sanctuaries and add to the challenge of HIV-1 clearance from them.