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Significant gastrointestinal pathology occurs in progressive HIV and simian immunodeficiency virus (SIV) infections. This review will examine the relationship between the detrimental events to the gastrointestinal tract during the acute phase of infection and disease progression through the chronic phase and, ultimately, AIDS.Gastrointestinal tract CD4 T cells are dramatically depleted in acutely HIV-infected humans and SIV-infected rhesus macaques, sooty mangabeys, and African green monkeys. In addition HIV infection of humans and SIV-infection of rhesus macaques are characterized by enteropathy and increased intestinal permeability. While SIV-infected rhesus macaques and HIV-infected humans manifest chronic and systemic immune activation and microbial translocation, and progress to chronic infection and AIDS, however, SIV-infected sooty mangabeys and African green monkeys do not.Recent studies have increased our understanding of the mechanisms relating structural and immunological damage to the gastrointestinal tract during the acute phase of HIV/SIV infection to immune activation and disease progression in the chronic phase.