Immune therapy that increases the rate of infected-cell clearance in the drug sanctuaries is another approach to stopping ongoing replication and could be encouraged through enhancing the function or penetration of CD8 T cells , natural killer (NK) cells or innate immunity . But unless clearance rates in the sanctuaries can be boosted beyond the rates observed in the main compartment, this approach alone is likely to be insufficient to halt persistent replication in sanctuaries where the effectiveness of antiretroviral therapy is also very low (Fig 5C). However, trafficking therapy and immune therapy can be expected to act synergistically so that treatments that combine a sub-threshold trafficking therapy and a sub-threshold immune therapy could be sufficient to halt replication (Fig 5D). Improving the penetration of antiretroviral drugs into sanctuaries is a third approach to tackling persistent replication that could work in synergy with these approaches (Fig 2).