Step Perspective, Volume 5, Number 1; A Publication Of The Seattle Treatment Education Project - February 1993
Douglas Arditti, M.N., ARNP

Wasting specifically refers to the loss of muscle protein often termed lean body mass(LBM). Studies have demonstrated that there is critical level of LBM necessary to sustain life. People with AIDS who begin to waste unchecked have significantly greater morbidity (incidence of illness or symptoms) and mortality (death) as they approach this level. Many measures exist to determine LBM, however the majority are often influenced by other factors such as drug therapy, other disease states, or adipose tissue deposition.

Total LBM can be determined by a number of specialized techniques that are available in research settings. These studies are often too laborious and require special technology not readily available in the clinical environment. It is clear that following the patient's weight regularly will give some indication of overall nutritional status, however this may not adequately reflect LBM in the seriously ill person with AIDS experiencing significant weight loss. Serum albumin and tricep-fold anthropomorphic measurements are two tests that are inexpensive, clinically available, and easy to perform that will assist clinicians in evaluating LBM in their patients.

Wasting can occur because of inadequate intake due to anorexia (poor appetite) and fatigue resulting from disease or medications. Given this scenario, a vicious cycle can occur in the seriously debilitated person as malnutrition often produces these very same symptoms. Thus the individual becomes increasingly malnourished because he/she has no appetite to eat or limited energy to purchase and prepare food. inadequate financial resources for food can further complicate this picture.

Studies have demonstrated that wasting due to malnutrition is the most common cause of wasting syndrome in people with AIDS. Therefore it is important that individuals and their health care providers pay close attention to nutritional status, intervening before wasting has become clinically evident. This intervention can be as simple as encouraging individuals to eat more, particularly foods which have a high caloric value and are 'nutritionally dense.' (I often refer to this as the Jewish-mother therapy.) Nutritionally dense foods are those with high calories and high nutritional value. Peanut butter and jelly sandwiches vs. a six pack of cola soft drinks are an example of this comparison.

Individuals who are more debilitated or who find eating large or frequent meals difficult, may benefit from dietary supplements. These come in many forms, examples being Ensure, Sustacal, Resource, Lipids, etc. However, dietary supplements are expensive and often not necessary. Consultation with a skilled and experienced nutritionist is invaluable in developing the best dietary prescription. On occasion, providing nutrition via a feeding tube or intravenously by hyper alimentation may be necessary to prevent or reverse severe wasting. Although these measures are often used as "last ditch" interventions , some clinicians believe that better results can be achieved if more aggressive measures are implemented in a timely fashion. This author's clinical experience corroborates these findings.

A number of pharmacological agents have been employed to reverse anorexia thereby improving the overall nutritional status of the person with wasting syndrome. Megesterol acetate (Megace) a synthetic progestin has been shown in a number of studies to improve appetite and increase weight in people with AIDS. These findings, though interesting, have not shown that survival was increased. This may be due to the fact that questions regarding Megace's effect on LBM were not answered. Many clinicians believe that weight gain is a result of fluid retention and increased fat deposition. It is important to note however, that many patients taking Megace reported improved well being. Significant side effects include deep vein thrombosis and gynecomastia (breast development) in males. Fortunately the incidence of side effects is very infrequent.

Dronabinol (Marinol), an oral preparation of THS, has also been shown to be beneficial in increasing appetite and weight gain*. Further study is warranted to examine whether Marinol has a better effect on increasing LBM when compared to megesterol and placebo. The most significant side effect was euphoria and sedation which improved with dose reduction. At this writing the author could find only limited data on anabolic steroids as a treatment for wasting syndrome in AIDS. Two studies currently in progress should be watched closely for any promising results.

Anorexia due to nausea can often be improved by adjusting medications (if these are thought to be the cause), altering food preparation to improve palatability, or adding anti emetic medications in severe cases. A nutritionist can be very helpful in providing information regarding food preparation to assure adequate nutrition and calorie intake.

Hyper metabolism (an increase in energy expenditure) and altered metabolism (an abnormal response to energy production and lean body mass conservation) are also contributing factors in wasting syndrome. A thorough review of the pathophysiology of these factors is beyond the scope of this article, though some important points will be reviewed.

Some studies have indicated resting energy expenditure is increased in asymptomatic HIV infected individuals**. Conflicting data does exist on this subject. For the clinically stable person it is unlikely that nutritional needs will vary significantly from un-infected individuals of similar age and activity level. Sound nutritional habits should be developed such as eating balanced meals high in complex carbohydrates with adequate high quality protein and micronutrients. Costly dietary supplements, such as enzymes, extracts, and megavitamins may not be helpful or necessary and should be viewed with caution. consult a qualified nutritionist for advice in developing a plan that is sensible.

Research studies have shown that individuals with acute or chronic infection often have elevated basel metabolic rates and therefore will require increased calorie and protein intake. Individuals with AIDS who have active disease are no exceptions. There are data however, suggesting that unless the underlying infection is treated, increasing intake will have little effect on increasing lean body mass. A study in patients with CMV or MAI disease showed that they continued to lose lean body mass despite nutritional repletion until they began appropriate antiviral or antimycobacterial therapy*. Therefore, immunocompromised HIV infected individuals who begin to lose weight should be carefully evaluated for infection or malignancy and appropriate therapy implemented in conjunction with a program aimed at nutritional repletion.

Cytokines, produced by the immune system, assist in mediating the host response to infection. Much has been written about cytokine abnormalities in people with AIDS and their possible role in wasting syndrome. Tumor necrosis factor (TNF), produced by macrophages, has been shown in some studies to be elevated in people with AIDS with wasting syndrome, however other studies have demonstrated high circulating levels of TNF without clinical evidence of wasting*. TNF has been shown in animals to induce anorexia thus impairing intake. The mechanism of wasting is thought to be due in part to altered metabolism of fat and protein. The derangement in fat metabolism results in continual fat breakdown and buildup without harvesting energy or building protein stores. This process, termed futile cycling, results in net loss of energy. In addition, normal host responses to starvation i.e., sparing LBM and conserving calories are also deranged. The host continues to break down LBM at a higher rate than would be expected in a host with diminished calorie intake.

Animal studies have demonstrated that TNF can cause severe wasting in healthy animals but over time they become resistant to its effects. Treatments with drugs such as pentoxifylline (Trental), shown to inhibit TNF *in vitro, have been disappointing. It appears that TNF alone is not sufficient to cause wasting but interacts with other cytokines such as interleukin -1 (IL-1) and alpha-interferon (alpha-IFN).

IL-1 also produced by macrophages, causes fever and protein wasting. It also plays an important role in stimulating other cells within the immune system. Circulating IL-1 is also present in people with AIDS, particularly during acute infections. It has also been shown to induce anorexia which may contribute to diminished intake of food, however as with TNF, animals chronically exposed to IL-1 become more resistant to its effects.

Alpha -IFN, produced by lymphocytes, in numerous studies has been shown to be elevated in both asymptomatic HIV -infected individuals and people with AIDS. It too has been shown to play a role in causing anorexia, including futile cycling, and increasing breakdown of LBM. Like the aforementioned cytokines, alpha-IFN does not appear to be solely responsible for wasting syndrome as many asymptomatic, healthy,. HIV - infected individuals have high circulating levels of this lymphokine.

Researchers theorize that the cytokines TNF and IL-1 released acutely (e.g., during infection), in conjunction with alpha - IFN work synegistically contributing to increased energy expenditure and metabolic alterations associated with wasting syndrome > It is important to note that all of these cytokines can contribute to anorexia and constitutional symptoms which, as mentioned earlier, are major factors in impairing intake. Continued research is warranted to further explain the role cytokines play in wasting in order that strategies can be developed to intervene, in hopes of preventing this vicious cycle from spiraling.

Malabsorption, impaired absorption of nutrients from the gastrointestinal (GI) tract, can also adversely affect the overall nutritional status of HIV - infected individuals. Although studies have demonstrated that HIV itself can cause some degree of malabsorption, in the majority of the cases it does not appear to cause serious problems in otherwise healthy individuals*. however, a number of opportunistic infections commonly seen in people with AIDS can significantly cause malabsorption, e.g., CMV MAI, cryptosporidiosis, and isoporiasis, as well as other enteric pathogens such as giardia, salmonella, etc*. Malabsorption may further compromise an individual just barely compensating with reduced intake due to anorexia or constitutional symptoms. Aggressive evaluation and management of these disorders should be employed whenever feasible to minimize overall impact on wasting.

Wasting syndrome is a complex, multifactorial disorder in people with AIDS. Clearly, impaired intake plays a central role in the development of wasting. Anorexia and constitutional symptoms, and malabsorption significantly influence intake and may be influenced by disease state, immunologic mediators, as well as medical therapies. Cytokines appear to play a role in the development of severe wasting however their exact mechanism is unclear. Aggressive, anticipatory nutritional management as well as prompt diagnosis and treatment of reversible processes are currently the cornerstone of management and prevention of the wasting syndrome.
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