Because productive HIV-1 infection predominantly occurs in activated CD4 T cells , it is implicit that HIV-1 infected cells are less permissive to egress cues compared to uninfected CD4 T cells that normally travel through the germinal center. This degree of difference would significantly reduce the impact of trafficking therapy compared with our model predictions that rely on the assumption that infected and uninfected CD4 T cells respond equally to trafficking therapy. Hypothetical mechanistic approaches to orchestrating T cell trafficking to germinal centers (S7 Text) would involve manipulation of pathways that are central to the immune response; for example S1P-S1PR1-mediated egress of immune cells from lymph nodes into efferent lymphatics . In chronic infection, virus-specific CD8 T cells are largely excluded from the germinal center  or are functionally impaired within it . Thus, a potentially effective adjunctive strategy for control of the viral reservoir would be to restore the ability of these cells to kill infected cells by blocking the PD-1/PD-L1 inhibitory pathway  or allow entry of functional antigen-specific T cells by directly engineering CD8 T cells to express CXCR5 