HIV/SIV Enteropathy

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Abstract
Evidence is increasing that HIV/SIV‐induced changes in the highly differentiated gut‐associated immune system play a central role in the pathogenesis of gastrointestinal manifestations in HIV/SIV infection. It has been shown in both humans infected with HIV and in nonhuman primates infected with SIV that a rapid, very early, and more pronounced loss of CD4+ T‐cells occurs in the mucosa in comparison to the peripheral blood. The loss of this important regulatory T‐cell subset might explain mucosal immunodeficiency with the consequence of opportunistic mucosal infections. In addition, there is evidence that small intestinal damage occurs independently of secondary infections (HIV/SIV enteropathy). In late‐stage human disease, HIV enteropathy is characterized by villous atrophy with hyporegeneration and dysmaturation of intestinal epithelial cells. In SIV infection of macaques, villous atrophy is a very early event; however, it is accompanied by crypt cell hyperproliferation. Early‐ and late‐stage enteropathy in immunodeficiency virus infection may represent two types of immunologically mediated mucosal transformation in which the number and state of activation of regulatory T cells determine whether hypo‐ or hyperproliferative villous atrophy occurs.

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