The enrichment of infected cells within secondary lymphoid tissue and lymph nodes suggest a critical role for these anatomical sites in sheltering persistently infected cells during therapy . HIV-1 RNA is particularly abundant in germinal centers within lymphoid tissue [31–33]. Regulatory mechanisms that prevent self-reactivity in the germinal center keep this microenvironment relatively safe from cytotoxic CD8 T cells and natural killer (NK) cells that target and destroy infected cells [34–38], thereby giving this unique tissue compartment immune privilege. This impaired protective immunity along with natural epigenetic silencing mechanisms and poor drug penetration allows the virus continue to replicate . As neither antiretroviral drugs, nor immune cells are able to fully abate ongoing cycle of replication in lymphoid tissue, other strategies need to be sought.