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HIV-1 infection is complicated by the presence of latently infected CD4 T cells as well as several anatomical reservoirs that present a barrier to eradication by current antiretroviral therapy. The early establishment of these reservoirs also presents a challenge to the development of preventive vaccines. This review will outline how HIV-1 evades the immune system and establishes latent infection, and will look at reasons why latently infected cells are not eradicated by the immune system. The HIV-specific immune responses in anatomical sanctuaries will be discussed.HIV-specific immune responses have been studied in several anatomical reservoirs including the gut-associated lymphatic tissue that appears to be a major site of viral replication during primary infection.HIV-1 evades the immune system during primary infection. Anatomical sanctuaries are seeded in primary infection, and extensive replication occurs at these sites before the development of HIV-specific CD8 T-cell responses. These responses are not capable of clearing infection.