AIDS is a diverse clinical syndrome that is induced by the Human Immuno Deficiency Virus (HIV). Primary characterization is increased susceptibility to opportunistic infection and certain cancers due to progressive destruction of the helper T-cell lymphocyte by HIV. Patients with AIDS exhibit numerous abnormal immunological features of cell-mediated and humoral immunity as shown in Table 1. HIV can also infect mononuclear phagocytes, particularly within the brain and lung, thus producing the central nervous system effects of HIV infection as well as the interstitial lymphocytic pneumonitis observed in pediatric AIDS¹. The depressed helper/suppressor T-cell ratio is the hallmark of the disorder. Immunodeficiency in AIDS is often further compounded by secondary opportunistic infections and immunosuppressive therapy². In fact, it has been proposed that cytomegalovirus, other viruses and disseminated mycobacterial infection may be cofactors with HIV for the full expression of the syndrome³. Infections often occur with multiple concurrent or consecutive organisms⁴. The definitive infections and oncologic diseases associated with I AIDS are outlined in Table 2.

 

Although over half the cases of AIDS reported are initially diagnosed with Pneumocystis Carinii⁴, the diagnosis is often preceded by a period of fever and weight loss. Gottlieb reported that patients complained of anorexia and intermittent diarrheal illness, but that these symptoms usually could not explain the degree of weight loss. The weight loss, anorexia, and frequent symptomatic involvement of the gastrointestinal tract observed at the time of diagnosis constitute major nutrition problems in AIDS management.

The gastrointestinal tract is intimately involved in the infectious status of the AIDS patient. Enteric infections are not uncommon and can be accompanied by debilitating diarrhea (primary or secondary) and nutrient malabsorption. Enteric organisms are furthermore implicated as a source of bacteremias and sepsis in the AIDS patient. Organisms that are normally classed as non-pathogenic may establish local infections or secondary bacteremias.

Specific immune factors, predominantly secretory immunoglobulin A (S-IgA), cooperate with non-immunologic defense factors to serve as the body’s first line of defense against intestinal pathogens. The collective components of the host mucosal defense system are listed in Table 3.

 

S-IgA is the major immunoglobulin found in secretions. In the intestine, 80 to 90 percent of the immunoglobulin-containing cells are IgA isotypes⁵. Two monomeric IgA molecules are joined together by a J, or joining chain, and both molecules are produced almost exclusively by IgA plasma cells in the lamina propria⁶. Local production of S-IgA occurs when the immunocompetent cells are stimulated by contact with bacteria or antigen and is highly regulated by T-Cell subsets. In the case of bacteria, the immune response may be evoked only after extensive contact and some degree of tissue invasion⁶. S-IgA neutralizes viruses and enterotoxins⁷, prevents the attachment of bacterial pathogens to intestinal cell surfaces^5,7, inhibits the motility of bacteria⁷, and inhibits macromolecular uptake by the gastrointestinal tract^5,7. These activities collectively shield the systemic and local immune responses by blocking the interaction of antigens with the mucosa and gut-associated lymphoid tissue. The integrity of the mucosal surface is further protected by the inability of S-IgA to fix complement efficiently or render bacteria susceptible to phagocytosis (opsonify), which are both inflammatory reactions⁶. S-IgA may also reduce the virulence of bacterial strains as demonstrated by its ability to eliminate the genetic coding for special adhesive structures that bind particular bacteria to the mucosal epithelium⁷. Infections of greatest concern are the enteric pathogens associated with S-IgA deficiency, such as salmonella, campylobacter, and giardia.

Gastric acidity plays an important role in the nonspecific mucosal defense system. Most enteric pathogens are pH labile⁸. Bacterial counts exceeding 100 colony-farming units are rarely found in the stomach⁹. Acid secretory activity within the stomach prevents the overgrowth of microorganisms in the upper gut. Gastric acid also initiates protein digestion, decreasing the amount of intact antigen that is emptied into the small intestine.^10,11

The upper small intestine contains relatively few organisms, whereas in the colon there are more than 400 species of bacteria; and concentrations may increase dramatically, particularly of anaerobes⁹. The normal gut flora deters the establishment of pathogenic populations by competing for substrates, creating an unfavorable pH and eH (oxidation-reduction potential) environment for pathogens and producing antibacterial substances¹⁰. The indigenous flora also appears to enhance the development of the immune system⁸.

Antibiotic therapy can destabilize normal gut ecology and thus can predispose the host to intestinal infection. Both oral and parenteral antibiotics have been associated with an overgrowth of clostridium difficile resulting indiarrhea⁹. Bacterial overgrowth leads to extensive patchy ultrastructural damage to the mucosa, possible. macromolecular absorption and sepsis, and widespread nutrient malabsorption¹⁰. Dietch and coworkers¹² have shown that, with thermal injury to otherwise healthy rats, bacteria which translocate across the intestinal wall into the mesenteric lymph node will invade visceral organs when the animals are subjected to experimental bacterial overgrowth or antibiotic therapy.

Normal intestinal peristalic movement is a major factor which limits bacterial proliferation and overgrowths^9,10. The action helps gastrointestinal fluid dislodge loosely attached bacteria from the mucosa and pass them into the colony. The process is aided by S-IgA on the mucosal surface forming complexes with bacteria¹¹. Opiates and antidiarrheals which diminish small bowel motility may actually contribute to the pathogenesis and/or perpetuation of infectious diarrhea. This mechanism has been implicated in shigellosis, salmonellosis, and antibiotic-associated diarrhea⁸.

The sledding of the epithelial layer (desquamation) is directly proportional to microbial burden on the mucosal layer. Desquamation favors the colonization of the more adhesive pathogens, which can continuously reattach to the newly exposed epithelial layer⁶.

The mucous blanket lubricates the entire mucosal surface and offers protection from digestive enzymes and the penetration of antigens, toxins, and microorganisms¹⁰. Specific binding sites on the mucous blanket can trap molecules, proteins, or infectious agents. It also acts as a binding matrix for S-IgA, countering the effects of normal peristalsis on immunoglobulin loss¹³.

Protein calorie malnutrition has been associated with thinning of the mucous membranes, decreased S-IgA, and altered gut flora which have been linked to an increased incidence of gastrointestinal infection^14,15. Impairment of mucosal immunity may contribute to AIDS enteropathy and predispose patients with HIV infections to mucous membrane infections, such as candidiasis, cryptosporidiosis, and pneumocystis pneumoniae^16,17.

It has been estimated that 50 percent of patients with AIDS have intestinal tract involvement¹⁸. In one series of 80 patients, 85 percent reported gastrointestinal symptoms, the most common complaint being diarrhea in 60 percent of these patients. Almost 40 percent experienced dysphagia and 20 percent, rectal pain¹⁹. Since the gut is a target organ in AIDS, numerous factors have been proposed that may contribute to gastrointestinal dysfunction. These include HIV transmission through the rectal area²⁰, high prevalence of enteric pathogens among homosexual males^21,22,23, and diminished secretory immunity due to collapse of normal T-cell regulation²⁴.

Figure 1 illustrates the diseases that may occur at various sites along the gastrointestinal tract,: profuse, chronic, watery diarrhea; nausea and vomiting; and abdominal cramping and malabsorption resulting from the protozoan cryptosporidium, which attaches to the epithelium of the small and large intestines. A similar clinical picture is caused by another protozoan observed less frequently, isospora belli, which invades the enterocyte cytoplasm. Mycobacterial infection is characterized by ineffective macrophages packing the lamina propria of the small intestine. Cytomegalovirus enteritis results in protracted diarrhea, weight loss, and other hemrorhagic lesions. Patients with AIDS are quite susceptible to infection with salmonella typhimurium, which may result in life-threatening diarrhea and recurrent bacteremia resistant to antibacterial therapy.

In 50 percent of patients with Kaposi’s Sarcoma, the bowel is involved^23,25. Although intestinal lesions are usually asymptomatic, their presence is associated with a shortened survival time²⁶. Diarrhea and severe protein-losing enteropathy have been reported with small intestinal Kaposi's Sarcoma²⁷.

Patients with debilitating diarrhea, who exhibit no evidence of an identifiable infectious agent or who experience persistent symptoms following an apparently successful microbiologic treatment of an identified pathogen, may he infected with the microsporidian Enterocytozoon bieneusi, an organism that requires electron microscopy of intestinal biopsies for diagnosis. Regardless, these patients represent a perplexing clinical dilemma in their management. A variety of histologic changes have been identified in what is termed AIDS Enteropathy, including nonspecific chronic inflammatory changes in the small intestine and colon^28,29-31. The intestinal architecture may show minimal or no disruption²⁹, ³⁰ or partial villous atrophy³¹.

Histologic changes and diarrhea may be accompanied by malabsorption. Increased fecal fat^28,29,31 and abnormal C-Glycerol Tripalmitin³⁰, vitamin B₁₂ Schilling's test²⁸, and D-Xylose absorption test^28,29-31 have been reported. Malabsorption is also seen in patients without diarrhea, suggesting it can be a subclinical process³¹.

Malnutrition is a serious problem in the AIDS patient, and its, treatment has been enigmatic. Severe losses of 20 to 40 percent of usual weight, depletion of body cell mass, and decreased serum proteins have been well described^33,33. Significantly depressed levels of blood seleniu³⁴ and serum zinc³⁵ have been reported, although it is likely that outer micronutrients are diminished.

Since the immune deficiencies in AIDS parallel those of protein-calorie malnutrition, numerous investigations have suggested that malnutrition may influence both the acquisition and course of the diseasc^36,37. However, no studies have evaluated the effect in nutritional intervention on the disease outcome. It is becoming increasingly apparent that the degree of tissue wasting likely Influences the time of death, and even clinically stable patients fail to replete body cell mass³⁷. Therefore, nutritional intervention appears justified as early as possible in the disease course. Those individuals presenting with an involuntary loss of 10 percent of reference weight should receive nutritional care beyond the standard hospital diet. Unfortunately, this type of practice is in contrast to the actual clinical practice found by O'Sullivan and coworkers³². Their survey of 50 malnourished patients admitted for AIDS revealed that 60 percent of these received no nutritional supplementation.

A major problem in developing appropriate nutrition strategies in AIDS management is the overall lack of information on the quantitative contributions of diminished nutrient intake, nutrient malabsorption, and altered metabolism to weight loss. It is interesting to note that anecdotal reports exist about the failure of parenteral nutrition to influence the outcome in AID³⁸. It is necessary to consider the composite of factors contributing to malnutrition, in order to determine the efficacy of nutritional therapy in an individual patient.

Patients with secretory diarrhea often present with significant electrolyte imbalances that must he corrected prior to the initiation of any aggressive nutritional support. Pectin-containing supplements or foods have been suggested to decrease diarrhea³⁹. Pectin, a soluble, noncellulosic fiber polysaccharide, has several effects on the gastrointestinal tract, including: (1) maintaining the morphology of intestinal vilii⁴⁰; (2) increasing lipase activity in the small bowel⁴¹, (3) delayed gastric emptying⁴², (4) increasing intestinal transit tim⁴³, and (5) promoting increased fecal production of short chain fatty acids (SCFA⁴³. It is possible that the addition of pectin to the diet increases the production of SCFA which, in turn, are necessary for the absorption of sodium by the colonocytes. This reduces the osmotic load of the colonic lumen and increases the absorption of water through an osmotic gradient to decrease the fluidity of the lumen and to prevent the formation of liquid stool⁴⁴.

Several diets have been utilized in the treatment of malnourished ARC/ AIDS patients. These diets often vary in their carbohydrate, protein, fat, branched chain amino acid, glutamine, mineral, vitamin, trace metal, pectin, and lactose content; required digestion and absorptive gut surface area; cost; and overall nutritional benefit. Presently, there is no clinically proven superior oral, enteral, or parenteral diet for either the inpatient or outpatient population. Most clinicians and nutritionists do agree, however, that an ideal ARC/ AIDS oral or nasointestinal enteral diet should provide low molecular weight protein in the form of polypeptides and contain minimal fat (less than 3 percent), a high concentration of branched chain amino acids (leucine, insoleucine, and valine) and glutamine (the preferential energy source of the small bowel), adequate mineral, vitamin, and trace metals (manganese, selenium, chromium, molybdenum, zinc, and copper), pectin, and no lactose. The ideal diet should also deliver 100 to 150 nonprotein carbohydrate calories per gram nitrogen, require minimal digestion and limited gut absorptive surface area, be inexpensive, provide maximal nutrition, and be consumed orally or via a small caliber nasointestinal feeding tube.