The gastrointestinal tract is a major target organ in Acquired Immunodeficiency Syndrome (AIDS). Patients with AIDS frequently present with diarrhea and weight loss sometimes unassociated with the presence of an infectious agent. The secretory nature of the diarrhea and other characteristics suggest that the HIV virus may interact with a receptor on mucosal cells, a receptor which recognizes the secretory peptide VIP, and which results in the generation of second messengers responsible for electrolyte secretion. Because the virus or other sequela of the disease may lead to the release of other peptide hormones, which induce intestinal secretion (namely, gastric inhibitory peptide, calcitonin, neurotensin, and bombesin), we propose to study the profile of these peptides prior to and during the course of diarrhea in AIDS or ARC patients. Having a better understanding of which peptide(s) is(are) elevated during a particular phase of the disease, will aid in our development of better and more specific therapy for this debilitating symptom.
A second aim of the present proposal is to study the effects of a synthetic somatostatin analog, SMS 201-995, in AIDS patients with diarrhea. This substance has been demonstrated to be effective against VIP- induced diarrhea in man. We believe that it is likely that this compound will inhibit the diarrhea in AIDS, regardless of whether it is of infective origin or is due to elevated levels of VIP or related hormones. Furthermore, because of similarities between the HIV protein coat and the amino acid sequence in VIP, we anticipate that SMS 201-995 will be effective therapy in patients found to have diarrhea of undocumented (HIV?) etiology. In summary, this project will provide important information as to which, if any, of the secretory peptide hormones are elevated in AIDS and whether or not intervention therapy with SMS 201-955, will be of benefit in preventing the diarrhea due to a particular peptide, opportunistic infections of the GI tract, or due to the action of HIV virus on the epithelium.
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