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The field of HIV vaccines received a "boost" with around 30% protection obtained in the RV144 randomized, double-blind, efficacy trial in Thailand. Currently, 560 clinical trials in HIV vaccine development are registered as complete and results are expected from several of these studies. The modest success attained at this time may be attributed to early attempts at identifying an animal model to test vaccine efficacy. Macaque models of HIV-1 infection have revealed viral infection, transmission, pathogenesis, and prevention. Identification of simian immunodeficiency virus (SIV) and its related strains served as the macaque counterpart of HIV and through genetic engineering, enabled chimera development that explored how macaques respond to a human antigen as well. Along with understanding viral infection, it is worth exploring the genetic repertoire of macaques for determining how the major histocompatibility complex and anti-retroviral restriction factors offer barriers to viral replication.