Antiretroviral therapy through barriers : a prominent role for nanotechnology in HIV-1 eradication from sanctuaries

In HIV-1 management, eradication of the virus from sanctuaries represents a major and challenging goal. The genital tract, gut associated lymphoid tissue, lymph nodes, central nervous system, macrophages and latently infected CD4+ T lymphocytes are typical sites where HIV-1 compartmentalizes. To circumvent this problem, a consistent number of studies have focused on improving ARVs (antiretroviral drugs) delivery into sanctuary sites and different nanotechnological approaches have been developed. Cellular HIV-1 sanctuaries (i.e. macrophages) can be reached by nanoformulation of ARVs or by activation of latently infected cells. Anatomical sanctuaries (i.e. brain or male genital tract) can be addressed by increasing the permeation of ARVs across tissue barriers, such as the blood-brain barrier or the blood-testis barrier, while ARVs concentration in lymph nodes can be enhanced by drug encapsulation in CD4-targeted nanoparticles.