In fact, a significant obstacle in HIV vaccine research has been the difficulty in developing an appropriate animal model with many of the features of human HIV infection. The only animals susceptible to experimental infections with HIV are chimpanzees, Pantroglodytes, and pigtail macaques, Macaca nemestrina. These animals maintain low levels of persistent virus but do not develop clinical manifestations of AIDS. In contrast, Asian monkeys, especially rhesus monkeys from India, are highly susceptible to SIVmac infection and progressively develop an immunodeficiency syndrome that is similar to human AIDS. Plasma viral levels during acute and chronic SIVmac251 infection in these animals parallel those observed in humans, with some animals containing virus spontaneously and progressing to disease slowly as in HIV-1 infected human long-term nonprogressors. In contrast, others maintain high viral loads and behave like human rapid progresses. As in HIV-1 infected humans, the cellular immune response to SIVmac during acute and chronic disease differs significantly, and evidence of immune escape has been well documented. This is particularly true of the mucosal immune system, especially the many CD4 CCR5 T cells in the gut associated lymphoid tissue, the major site of the viral replications and of CD4 T-cell depletion in SIV-infected macaques. This also mimics the human diasease and thus the SIV macaque model is currently considered the most appropriate animal model for studies on potential protective immune responses against HIV.