Human immunodeficiency virus and the gastrointestinal tract

Abstract

Human immunodeficiency virus (HIV) is a retrovirus infecting CD4 positive cells, causing profound immunosuppression and eventually manifesting clinically as the acquired immunodeficiency syndrome (AIDS). The cells principally infected by HIV are T4 (helper) lymphocytes and macrophages. The eventual loss of helper cell function is the prime reason for immunodeficiency, which renders the individual susceptible to opportunistic infections. Virtually every organ system in the body can be affected clinically during the course of HIV infection. The gastrointestinal tract is a major target and the physiological sequelae are an important cause of morbidity and mortality. The pathophysiology of intestinal infection is not yet fully understood but two main mechanisms have been postulated. The first is reduced intestinal immunity resulting in chronic opportunistic infections, which themselves cause altered intestinal function. The second is that HIV per se affects the intestinal mucosa, causing malfunction. The mechanisms by which the latter occurs are controversial but may result from either direct infection of mucosal epithelial cells or from macrophages within the mucosa. Reports have documented the presence of the HIV genome in both epithelial argentochromaffin cells and macrophages. In addition, profound degeneration of intrinsic jejunal autonomic neurones has been demonstrated but the functional significance of such denervation is as yet unknown. The clinical stage of HIV infection at which intestinal mucosal immunity fails is, by definition, when opportunistic infection occurs (that is, clinical progression to stage 4 disease, namely AIDS) but detailed knowledge of the aetiology of intestinal immune failure is lacking. However, protection of intestinal mucosal surfaces with antibodies against HIV, induced by vaccination using the oral or rectal route, is an area of great interest. The major site of entry of HIV is thought to be via the intestinal tract and thus protection of its surfaces may be crucial in preventing infection.