Wasting guide

by Tadd Scott Lazarus, m.d. and David W. Purdy

A guide for physicians, patients and other healthcare providers about fighting AIDS-related wasting syndrome

The goals of these guidelines are to help physicians and patients with the decisions they need to make regarding the use of hormone therapies in the treatment of HIV. The goals are: To prevent HIV-related wasting by administering low hormone level tests To treat low hormone levels or hypogonadism, a precursor to wasting To successfully treat HIV-associated wasting To help HIV-positive persons become longer-term survivors with the highest quality of life

Loss of lean muscle, or wasting, is one of the most common complaints of people with HIV or AIDS. The Centers for Disease Control (CDC) defines a person with wasting as being 10% below normal body weight or suffering from an unexplained decrease in body weight.

Wasting is the second leading HIV/AIDS related cause of death in the U.S., and third leading cause of death in the world, according The Centers for Disease Control Surveillance Report 1996, published by The World Health Organization.

Symptoms commonly associated with wasting include weight loss, fatigue, depression, poor appetite, chronic diarrhea, malnutrition and sexual dysfunction.

Malnutrition occurs frequently during HIV infection, increases with disease progression and strongly predicts patient survival, independent of CD4 T-lymphocyte counts.¹ Experts agree that the perceptible loss of lean muscle tissue occurs at many points in the spectrum of wasting caused by HIV and that severe weight loss accompanies many neoplastic diseases such as Kaposi's sarcoma (KS) and lymphoma. This is often simplistically ascribed to the catabolic effects of chronic HIV infection.²

The immune system is also impaired by HIV-related malnutrition. Altered metabolism, inadequate intake and malabsorption compound the effect of wasting. Other factors contributing to wasting syndrome include the effects of chemotherapy, abnormalities of carbohydrate, fat and protein metabolism and the cytokine response.³

Regardless of the mechanism of the loss of lean muscle tissue in HIV positive patients, the resultant catabolic state undoubtedly contributes to the already present immune deficiency and therefore negatively influences the course of the disease.⁴ In fact, it may contribute to AIDS itself.⁵

Wasting could be the most expensive part of the overall healthcare of an HIV positive person. The overall wasting state also contributes significantly to a downward spiraling effect of the patient into a state of susceptibility to a new or occurring opportunistic infection.⁶ Wasting also means that the response to treatment of these opportunistic infections will be blunted. Studies show that loss of lean muscle mass is directly correlative to mortality.⁷ Since death from wasting is ultimately related to the magnitude of tissue depletion, restoration of body cell mass may enhance survival.⁸

Hypogonadism and Its Correlation to Wasting
Hypogonadism (low testosterone level) is common in men with HIV infection.⁹¹⁰ In fact, a number of studies show that more than half of male HIV/AIDS patients with CD4 absolute number <50 are hypogonadal.¹¹¹² Experts now agree that not only is the hormone/endocrine system involved during HIV infection¹³, but that wasting itself is a direct result of hormone deficiencies in the patient living with HIV.¹⁴

In a study trying to determine the correlation between wasting and hypogonadism in the HIV positive person, it was determined that wasting patients had significantly lower total and free testosterone levels than HIV patients who were not wasting. Both groups, however, had similar and higher mean CD4 counts.¹⁵ The possible factors leading to hypogonadism in HIV-infected men include HIV infection itself, opportunistic infections, chronic debilitating illness, and effects of cytokines on the hypothalamic-pituitary-gonadal axis.

Whatever the etiologies are, hormonal deficiencies negatively affect metabolism and cause the body to lose vital nutrients. This causes or fosters chronic fatigue or exhaustion. Hypogonadism is also correlated with T-lymphocyte depletion and weight loss.¹⁶ Hormonal deficiency states may cause abnormalities in immunity and lead to susceptibility to a variety of viral, bacterial and fungal infections.¹⁷

The principal anabolic steroid is testosterone. It would appear logical to prescribe testosterone for hypogonadism or a low testosterone serum level. However, it is widely known that injectable testosterone is highly androgenic. The androgenic properties are the masculinizing properties of anabolic steroids. It is the androgenic properties, many experts feel, which are primarily responsible for many of the potential side effects associated with anabolic steroids. Experts now suggest that it may be more appropriate to prescribe anabolic steroids that are higher in anabolic properties and lower in androgenic properties, such as oxandrolone or nandrolone decanoate. Many physicians who specialize in HIV are now prescribing more androgenic anabolic steroids, instead of testosterone for wasting, with excellent results and no apparent significant side effects.

Because treatment of hormonal abnormalities of HIV is often effective, improved diagnosis and appropriate therapy of these abnormalities will result in improved quality of life and, possibly longer survival of patients with AIDS.¹⁸ Further studies are needed to clarify the causes of hypogonadism in HIV, its clinical significance, treatment, relevance to the progression of HIV infection and influence on the immune system.¹⁹

A number of HIV positive persons throughout the course of the disease may experience sexual dysfunction. This can be both embarrassing and frustrating and can affect the patient's overall quality of life. Data support the contention that specific hormones, such as testosterone and anabolic steroids, actually enhance sexual desire.²⁰ Many physicians have often asked "why should we intervene to make a person with HIV have a greater sex drive?" Their concern is that this would lead to an increase in unsafe sexual behavior. Of course, there is no correlation between the two. The answer is that no person has the right to deny an HIV positive person the right to expression of his or her sexual needs and desires. But all physicians and healthcare workers have the responsibility to reinforce the message of safer sex, especially when an intervention (e.g. antidepressants or androgenic agents) will restore sexual desire and functioning.

Resting energy expenditure (REE) is the energy that an individual consumes at rest to maintain body functions. A study done by Carl Grunfeld, M.D. revealed that HIV positive, asymptomatic men with CD4 absolute number in the range of had a 12-20% increase in REE. That would infer that without any other factor present but HIV infection; the patient should consume 12%-20% increase in calories everyday as compared to their HIV negative counterparts. The degree of resting energy expenditure on body composition, although not a constant feature of HIV infection, is more likely to occur during HIV weight loss. Thus, increased resting energy expenditure appears to contribute to wasting if it is not offset by an appropriately increased caloric intake.²¹ A study published in The New England Journal of Medicine in July of 1995 stated that the true determinant of energy balance is not resting, but total energy expenditure (the difference between energy intake (food/calories) and output). The study went on to say that during rapid weight loss, total energy expenditure was reduced, primarily because of reduced physical activity and reduction in energy intake. In conclusion, reduced energy intake (not eating enough food), not elevated energy expenditure, is one of the prime determinants of weight loss in HIV-associated wasting during concomitant illness.²²

Prevention
Testing for potential low testosterone serum levels, or hypogonadism, is one of the most significant preventive measures instituted by physicians for the prevention of HIV wasting and weight loss. The recognition of hormonal disorders is essential for optimal therapy because, if it goes unrecognized, their evolution is dramatic.²³ It is quick and easy to determine if a male patient has signs and symptoms of hypogonadism by asking the following questions:

1. Do you have a reduction in the number of sexual thoughts and/or the desire to have sex (reduced libido)?
2. Do you awaken with a morning erection?
3. Are you able to achieve and maintain an erection during sexual activity?
4. Are you able to ejaculate?

Any change in sexual functioning should elicit a search for a cause. Endocrine work-up should include an age-adjusted free and total testosterone as well as thyroid function tests. It is important to remember that depression can be causal and should also be ruled out.

If the patient is found to be hypogonadal, hormone replacement therapy should begin immediately.

Millions of healthcare dollars could be saved if every HIV-positive man worldwide were to have a testosterone serum level test administered. An early diagnosis would prevent a majority of debilitating conditions that accompany HIV wasting and weight loss. At the very least, a baseline measure for potential future hormone therapy would be noted in the patient's medical records.

Nutritional strategies should also be instituted to help prevent wasting, including early nutritional intervention with oral supplements, appetite stimulants²⁴ and exercise. A registered dietician should be consulted for more information regarding appropriate strategies.

Interventional Strategies
A number of factors should be considered before deciding what type of intervention to make for a person with wasting.

Laboratory Results
As noted earlier, every male HIV patient should have an age-adjusted free and total serum testosterone level test administered. This will not only determine whether the patient is hypogonadal, but will also record a baseline measurement. A general normal range for patients is as follows (but remember that the reference range must be age-adjusted and varies with each laboratory):

Appetite Stimulants
Appetite stimulants may lead to weight gain.²⁵ It is important to remember that appetite stimulants, Dronabinol and Megestrol Acetate, treat symptoms and do not alter the inability of the AIDS patient's metabolism to effectively oxidize fat and stop utilizing lean muscle as an oxidative substrate. With that said, not all anorexia heralds wasting. appetite stimulation is an important part of a multi-drug, multi-modality approach to weight loss and wasting in the setting of HIV infection.

Note, though, that researchers and clinicians have recognized the appetite stimulating effects of anabolic steroids for a number of years, so they should be considered to stimulate the appetites of patients suffering from hypogonadism or wasting as well.

In addition, one study showed that some appetite stimulant products are synthetic progesterones and have glucocorticoid activity at high dosages.²⁶ It is well known that glucocorticoids are immunosuppressive.²⁷

Hormones in Prevention and Treatment of Wasting
In 1984, in West Hollywood, California, a physician noted that his AIDS patients who were bodybuilders did not succumb to the onslaught of opportunistic infections that were afflicting his other AIDS patients. After a series of one-on-one interviews, he discovered a common element that separated the two groups. Those bodybuilding AIDS patients who were doing well were using hormones like anabolic steroids as part of their overall exercise regimen.

Those findings were first published in the journal AIDS Patient Care in April of 1993 and helped hormone therapies reach the forefront of HIV healthcare. This single observation also helped change the negative attitude surrounding hormones such as anabolic steroids in both the clinical and research setting.

Today, thousands of HIV/AIDS patients are prescribed hormones by their physicians for the treatment of wasting or hypogonadism. Many patients refer to the treatment as the reason they have a "new lease on life" and a major contributing factor to their overall higher quality of life. Researchers now admit that hormonal therapies may actually alter the course and progression of the HIV disease, although why this happens is not clear.

Controversies Surrounding Hormone Therapies
Hormone therapies would appear to be an obvious weapon in the treatment of HIV to stall or combat wasting. Unfortunately, access to the treatment was in the past stalled primarily because of the controversies that surround these agents, largely due to the widespread abuse of anabolic steroids by bodybuilders and athletes. To further complicate matters, Congress passed The Anabolic Steroid Control Act of 1990. Not only did this law immobilize physicians to prescribe anabolic steroids, but also experts now acknowledge this probably set back the research of these medications by decades.

Today, hormone therapies are considered not only valid and legitimate, but a front-line treatment for people living with HIV. There now appears to be a positive attitude emerging regarding these medications in the medical community.

The end result is not only a victory for people with HIV, but also people suffering from cancer and other progressive, debilitating diseases. Research on these therapies is still limited and should be encouraged and supported.

Safe Use of Anabolic Steroids and Liver Function
All steroids are metabolized by the liver and thus carry class warnings in the drug information insert concerning hepatotoxicity (liver toxicity). Despite what has been discussed in the past, anabolic steroids themselves have not shown significant toxicity when prescribed at therapeutic dosages, and hepatotoxicity has been associated with just a few of the many available anabolic steroids.

There have been a few anecdotal reports of liver function problems in anabolic steroid-abusing athletes, who increase the risk of potential side effects by combining injectable and oral anabolic steroids and at doses 10 to 40 times greater than those prescribed therapeutically. Interestingly, even under these circumstances, there have been only rare reports of severe or life-threatening side effects in athletes and bodybuilders who have abused anabolic steroids.²⁸ In a placebo controlled study, no negative effects were seen in liver function after anabolic steroid administration.²⁹

Overall, it appears that liver damage should not be considered a property of anabolic steroids.³⁰ Thus, the scare tactics used during the anti-anabolic steroid years regarding severe health hazards of anabolic steroids have been exaggerated.³¹

One study suggested that one anabolic steroid, oxandrolone, actually diminished the severity of the liver injury in patients with severe alcoholic hepatitis and suggested that anabolic steroids should be added to the patient's treatment.³² In another placebo-controlled study, results showed that there was no statistical difference between hepatotoxicity in patients treated with oxandrolone versus those on placebo.³³

Overt liver damage has been occasionally associated with the long-term use of some, but not all, oral anabolic steroids. The damage occurs because they are 17-methylated or alkylated. Oil-based injectable anabolic steroids do not have this property.³⁴³⁵ This potential negative side effect is also noted in the long-term use of 17-methylated estrogen steroids used as contraceptives, Such as the birth control pill.

The effect of anabolic steroids on heart function has also been studied. In separate controlled studies, there were no detectable differences in heart measurements in weight training athletes who used anabolic steroids and those who did not.³⁶³⁷ Blood pressure at rest and during exercise in weight lifters who used anabolic steroids was also studied, concluding that blood pressure remained insignificantly elevated and that the slight elevation may be a result of the circumference in the larger arm mass of weight lifters.³⁸

Potential Side Effects of Steroids
The following is a list of potential side effects associated with anabolic steroids. They include: rare hepatocellular neoplasms, cholestastatic hepatitis, edema, serum cholesterol increases, serum triglyceride decreases, acne and gynecomastia. All androgenic side effects are dependent on the dose and the androgenicity of the compound. Reported side effects are usually reversible.³⁹

Gynecomastia, is the excessive development of the male breast tissue often first noticed as a hard thickening under the nipples, is a negative side effect usually seen after the administration of high dosages of anabolic steroids for long periods of time.

Safe Use with Other Medications
Anabolic steroids do not compete with other medications for binding sites and are neither nephrotoxic or cytotoxic.⁴⁰ Anabolic steroids are not associated with anemia or granulocytopenia, as seen in AZT therapy.⁴¹ Some anabolic steroids, such as oxandrolone and nandrolone decanoate, have actually been shown to be immune stimulating.⁴²⁴³⁴⁴

Women and Anabolic Steroids
Wasting syndrome is actually more common in women than men.⁴⁵ While there are only a few controlled studies focusing on the use of anabolic steroids in the treatment of women, they have been shown to be an effective treatment of weight loss in women.⁴⁶ Anabolic steroids also have a long history of use in women suffering from osteoporosis.⁴⁷

The potential for significant side effects in women taking steroids is greatly reduced when using less androgenic anabolic steroids, like oxandrolone. Oxandrolone appears to undergo little overall metabolic transformation in the liver and is not only well tolerated in women, but also in men.⁴⁸ Stanozolol (Winstrol) is another anabolic steroid that has been prescribed safely for women. It appears to be a bit more androgenic than oxandrolone, but is well tolerated when using therapeutic dosages of 8 mg a day or 42 mg per week.

The protocols outlined in this guidelines report should be followed in the treatment of women as well as men. However, it is important to carefully monitor women who are being prescribed predominantly male sex hormones, such as anabolic steroids. Anabolic steroid-abusing female bodybuilders have reported hair loss, deepening of the voice and other masculinizing side effects. Other potential side effects may be similar to those seen in men.

Children and Hormone Therapies
There is a long history of treating children with hormone therapies, but special care should be taken in these instances, especially in monitoring for potential negative side effects. Nonetheless, anabolic steroids in particular have proven to be successful in the treatment of protein depleted children. ⁴⁹

Kaposi's Sarcoma and Hormone Therapies
There have been a few anecdotal reports in the past that anabolic steroids and growth hormone may cause Kaposi's Sacrcoma (KS) to foster or grow. There are a number of patients with KS who have been carefully monitored while being prescribed anabolic steroids and growth hormones. There is no evidence that anabolic steroids help spread KS. Regardless, it is still appropriate to carefully monitor the patient who has KS and who is being prescribed anabolic steroids or growth hormone.

Other Therapeutic Uses and Actions of Anabolic Steroids
Anabolic steroids play a major role in the regulation, growth and development of cellular composition of almost every organ throughout the body.⁵⁰⁵¹ Anabolic steroids also possess anti-catabolic (preventing breakdown) properties.⁵² One of the mechanisms of anabolic steroids is that they are effective in helping the body synthesize protein more efficiently, thus helping in combating wasting.

Anabolic steroids can also abolish a negative nitrogen balance in the body: a condition that can be created by wasting disorders, surgery, trauma and the administration of corticosteroids. ⁵³⁵⁴

Anabolic steroids help stimulate the body's own natural growth hormone and insulin-like growth factor production. They are also prescribed worldwide to help stimulate bone marrow production of new blood cells and used to treat autoimmune disorders, a common occurrence in the course of HIV disease.⁵⁵

Age-related muscle wasting has been shown to be a result of a decline in the body's protein synthesis rate. This phenomenon contributes to what experts now consider to be a form of male menopause called veropause. Again, it is well known that anabolic steroids help in protein synthesis.⁵⁶ It has been hypothesized that Alzheimer's disease, ALS and Parkinson's disease may be related to steroid hormone deficiencies.⁵⁷

Anabolic steroid therapy is efficient in the treatment of moderately severe aplastic anemia⁵⁸ and is beneficial in treatment following chemotherapy for certain cancers.⁵⁹

In a placebo-controlled study, anabolic steroids have been shown to be effective in enhancing fat-free mass and respiratory muscle function in patients with chronic obstructive pulmonary disease, without causing adverse side effects.⁶⁰

Anabolic steroids are also helpful in the treatment of cancer.⁶¹ For patients receiving chemotherapy for their cancer, nandrolone decanoate significantly helped reduce the number of blood transfusions, and there was no toxicity at 200 mg per week.⁶²

Immune Function Immune Function and Anabolic Steroids
A number of studies show that specific anabolic steroids can act as immune stimulants⁶³, influence immune function⁶⁴⁶⁵ or enhance the immune response.⁶⁶ One study showed that oxandrolone significantly improved lymphocyte numbers in patients with severe alcoholic hepatitis.⁶⁷ Another study showed that the number of lymphocytes were increased after prescribing nandrolone decanoate.⁶⁸ An early study in particular demonstrated that nandrolone decanoate enhanced macrophage activity and cell-mediated immunity in patients with uterine cervical cancer.⁶⁹

A 1993 study published in Clinical Immunology and Immuno-pathology suggested that sex hormones, specifically anabolic steroids, enhanced immune function and the CD8 cells significantly.⁷⁰ Many experts now feel that the CD8 T-cells have been undervalued in terms of the survival of patients with AIDS.

A study published in the American Journal of Pathology concluded that sex hormones influence the onset and severity of immune-mediated pathological conditions by modulating lymphocytes at all stages of life. The study's investigators added that the use of sex hormone modulation of immune responses for the treatment of autoimmune disorders is a promising area for future investigation.⁷¹ A study titled "Regulation of the Immune Response by Sex Hormones," concluded that sex steroids may have a role in the pathogenesis and treatment of some autoimmune disorders.⁷²

A few isolated studies have begun to examine the effect of sex hormones on the immune system and autoimmunity.⁷³ In the meantime, it appears that the status of the immune system will depend to some extent upon the net effect of the changes in the equilibrium of various hormones.⁷⁴ The manipulation of sex hormones may be used to modify the expression of autoimmunity.⁷⁵ This is a potentially promising area in the treatment of HIV.

Immune Function and Glucocorticoid Therapies
Interaction between the immune and endocrine systems is highly complex.⁷⁶ Studies have established that glucocorticoid steroids, such as cortisone, which are not anabolic steroids, are known to suppress the immune system.⁷⁷⁷⁸ Also, glucocorticoid steroidsnot anabolic steroidsmay actually enhance HIV replication.⁷⁹ Unfortunately, many physicians confuse glucocorticoid steroids with anabolic steroids.⁸⁰

Cytokines, Lymphokines and Anabolic Steroids
Cytokines help regulate immune response and function.⁸¹ Studies show that sex hormones have the potential to regulate cytokine gene expression in cells possessing the appropriate steroid receptors⁸², and may facilitate immunity by regulating lymphokines produced by helper T-cells.⁸³

Quality of Life
Literature on long-term survivors living with AIDS is replete with anecdotal evidence linking survival to such things as: (a) holding a positive attitude and perception of physical health; (b) participating in health-promoting behaviors; (c) engaging in spiritual activities and (d) participating in exercise.⁸⁴

Many patients believe that their diminishing quality of life may be a direct result of the numerous medications they are prescribed. The intrusive nature of multiple antiretrovirals and prophylactic medications is obvious.

Overall quality of life is not only a major concern for most HIV positive people but it is considered by many to be as critical a determinant of treatment strategies as is efficacy. Hormone therapies have been shown to not only improve patients' quality of life, but also help to create a more positive outlook and sense of well-being.

Specific hormones such as anabolic steroids historically have been prescribed because of their psychological benefits. In the past, the HIV positive patient who was wasting also had to endure the psychological trauma of witnessing their bodies transform into frail shadows of their former selves. Looking in the mirror or standing on a scale became a painful experience.

The dramatic positive effect that hormone therapies have on the patient's outward appearance has a direct correlation with feeling much better on the inside. Leaving the house fearful of what people might say or think becomes less important. Thousands of patients following hormone therapies for their wasting condition have already announced that they feel like they have a new lease on life.

Lean Body Mass
Lean body mass is the most important determinant of whether a patient is actually wasting. Therefore, it is important to assess the patient's lean body mass with state-of-the-art measurement devices such as bioelectrical impedance analysis (BIA).

Using a common scale is not considered accurate when assessing lean muscle tissue because it is not uncommon for people with HIV to continue to lose lean muscle tissue even though the body weight remains unchanged due to increase in fat.

Factors which contribute to wasting syndrome include abnormalities of fat and protein metabolism and the cytokine response.⁸⁵ Lean muscle is utilized inappropriately as a fuel source and fat is unable to be oxidized as an appropriate fuel source. That is the basic metabolic derangement that is at the heart of the wasting syndrome.

Studies have demonstrated that instituting nutritional supplementation alone for patients who are wasting appears to increase unfavorable fat mass. Patients who are prescribed anabolic steroids with nutritional support, however, gained more favorable fat-free mass without causing adverse side effects.⁸⁶ One anabolic steroid, oxandrolone, has been shown to actually decrease abdominal fat, in comparison to injectable anabolic steroids such as testosterone or nandrolone decanoate.⁸⁷

Nutrition
Careful dietary management is essential to avoid further compromising the immune status of the person living with HIV/AIDS.⁸⁸ Weight loss can be preventable and treatable, especially when it is identified early.

Unfortunately, most physicians have not received formal education in nutrition, according to the American Society of Clinical Nutrition. This can lead physicians to neglect or ignore available recommended nutrition guidelines. To compound the problem, most patients believe that their overall nutritional needs are actually being met through their daily diet. Of course this may not necessarily be the case. For HIV patients, a diet that includes nutritional supplements as well as protein enriched foods or protein supplements, will help ensure the overall success of hormone therapies.

Patients should consult a registered dietician qualified to help them develop the most appropriate balanced diet, especially considering the definition of "appropriate" and "balanced" may be a bit different for every patient. Also, a diet that is reasonable for one person would likely be inappropriate for another. Before one sees a registered dietician for the first time, complete a food diary for a couple of days. Oral nutrition supplements are cost-effective and safe and should be employed whenever feasible for the prevention and treatment of malnutrition. Unfortunately, most insurance carriers do not pay or cover the costs of these supplements and have created barriers towards their acquisition that can lead to a delay of many weeks before a patient gets their first shipment of a liquid nutritional supplement. Be prepared: at the first signs of anorexia or weight loss, nutritional supplements should be ordered. While awaiting their approval, the best alternative is to buy a protein powder from the health food store and use a blender so that caloric and protein intake can be immediately augmented.

Overall, the indications for nutritional support in AIDS patients are the same as in any other chronic disease. Providing appropriate nutritional support to AIDS patients is fundamental to optimal medical care.⁸⁹

Protein Intake Is Vital
Hormones such as anabolic steroids work by helping the body more efficiently synthesize protein, which is the building block for the growth of lean muscle tissue. Therefore, increased protein intake must be included as part of an entire hormone therapy regimen. In addition, it is imperative that persons with HIV and HIV-related wasting adhere to a consistent balanced diet.

Experts recommend that one gram of protein be ingested daily per pound of the patient's ideal body weight. For example, if a patient is 5 feet 10 inches and 144 pounds, and desires a healthier ideal weight of 170 pounds, he should ingest 170 grams of protein daily. An ideal eating schedule might include 3 meals (35 grams of protein per meal) and 2 protein supplement drinks (35 grams of protein per drink) per day.

While protein is found in many different foods, it would be rather difficult and tedious to try and eat 170 grams of protein strictly from the different food groups without the aid of a protein supplement. Protein supplement drinks are a convenient way to get necessary additional protein in the patient's diet. There are many different kinds of protein supplement products on the market today. Patients can purchase ready-made protein supplement drinks or buy protein powders and make the drinks themselves at home. Soy based products are now available for those patients who are lactose intolerant.

Experts believe it is best to take a protein supplement drink within 30 minutes before or after exercising or as a snack between regular meals. It is not recommended to use the drinks to replace three balanced meals each day.

It is absolutely critical to keep in mind that if a patient has a history of renal problems, there may be a need to lower overall protein consumption. A primary care physician or a registered dietician should carefully follow the overall amount of protein to be ingested.

Water
Experts highly recommend that people with HIV drink distilled water to help prevent the contraction of cryptosporidium, which is found in much of the world's water supply. Some of the newest in-home water filtration devices are approved for filtering this pathogen from the water supply.

Total Parenteral Nutrition
Total parenteral nutrition (TPN) is the provision of all or part of a patient's nutrients intravenously utilizing a wide bore catheter. The introduction of Total Parenteral Nutrition (TPN) in the treatment of malnourished and wasting patients, and patients with unusable gastrointestinal tracts, has become commonplace throughout the world.⁹⁰ It can be used with enteral therapies in a balanced approach to allow a slow introduction of enteral formula and still satisfy the body's caloric and nutrient demands. TPN therapy, however, appears to incur many risks and significant costs. Infection rates are reported to be higher in patients receiving TPN, and TPN use is associated with a range of metabolic problems. The overall catabolic state of many intensively treated patients who receive TPN may not be adequately reversed. Recommendations for TPN use in pediatric oncology patients include using TPN formulas containing glutamine to stimulate anabolism and TPN timing cycles.⁹¹ A 1993 study analyzing the cost of TPN for an average of 16.15 days before and after surgery reached $3,921 in total.⁹²

Crucial to the decision-making process for the initiation of TPN is the determination if enteral feeding can supply the totality of nutritional needs for a specific patient. If the answer is no, then TPN often provides the interim and, in some cases, long-term nutritional solution to the problem of nutritional support in a patient whose gut is unable to absorb nutrients sufficient to supply his or her needs.

A 1995 study found that the use of TPN has increased considerably in recent years, resulting in greater demands on human and material resources.⁹³ A review of literature suggests that TPN is only sometimes effective and that it actually produces measurable harm by increasing complication rates in certain groups of patients. However, there are still strong advocates for its use. The economic and ethical implications of TPN suggest that a continuous assessment of healthcare technologies, particularly those that are high-cost and high-risk, is critical to the overall quality of healthcare.⁹⁴

From a pragmatic viewpoint, the physician must diagnose, treat and intervene with the appropriate means for the gut to be used as fully as possible as the route of nutritional support. Often it is overlooked that the gut has important endocrine functions that are suppressed when feeding is not accomplished in that route. Finally, the patient should be evaluated (when appropriate) for the endoscopic placement of gastrostomy or jejunostomy feeding tubes so that a non-volitional, gut feeding route can be established.

Exercise
Exercise is extremely important and should be included any plan for a patient to prevent and treat wasting. Exercise helps ensure optimum results of the hormone therapies by helping the body maintain and restore lean muscle tissue.

One study noted improvements in health among individuals who attended scheduled exercise sessions.⁹⁵ Another study concluded that HIV-positive men, including those symptomatic for AIDS-related complex, can experience significant increases in neuromuscular strength and cardiorespiratory fitness without changes in T-lymphocytes or clinical diagnosis when an exercise regimen is prescribed and monitored according to American College of Sports Medicine guidelines for healthy adults.⁹⁶

Resistance exercise, not aerobic exercise, is considered the best form of exercise to build lean muscle tissue. Free-weight training, exercise-machine weight training are among the more popular kinds of resistance exercise programs. People fighting wasting should choose one that best fits their needs, physical abilities and overall schedule.

Although, under normal circumstances, aerobic activity should be included as part of the exercise program, the goal is to increase lean muscle tissue; therefore, it is highly recommended that focus be on resistance exercise or weight training.

Recent studies have also determined that exercise may activate the immune system, but that if it becomes too strenuous, the exercise may be immunosuppressive. What is correct for an individual is the level of exercise wherein there may be soreness but not fatigue. The patient should be encouraged to listen to his or her own body and exercise accordingly. The research in the area of exercise and AIDS is at its most nascent stages of development but it is widely acknowledged that exercise will be the critical "missing link" in wasting prevention and treatment.

Before beginning an exercise program, patients should have a complete physical examination and consult a certified exercise trainer.

Follow Up When to Cease Treatment
If a patient has successfully restored the lost lean muscle tissue and his or her body weight is back to normal, then it is appropriate to cease hormone therapy. It is important, however, to continue to monitor the patient's body weight and lean muscle tissue stores. It is also recommended that the patient continue an exercise regimen to help keep the lean muscle tissue.

Some argue that it is appropriate to continue the therapy, to keep an extra store of lean muscle tissue, in case the patient begins to waste at a later date. Currently, increasing a patient's lean muscle tissue stores above what is considered normal is not recognized as a legitimate medical practice and could be construed as bodybuilding or abuse of the hormone therapy for aesthetic purposes. This practice may in fact prohibit the effectiveness of the treatment in the long term. Most importantly, such practice is considered illegal under current law.

As stated previously, male hypogonadism can have many etiologies.⁹⁷ Reduction in viral load or treatment of an opportunistic infection can alleviate the cause and the patient may no longer require testosterone replacement therapy. These patients should be reassessed after a washout period to determine their gonadal hormone status through a free and total testosterone measurement. Other patients, usually with the lowest pre-treatment testosterone levels may have had HIV-induced destruction of the hormone producing tissue of the testis and may need long-term hormone therapy. In any case, only a combination of a post-treatment testosterone measurement while following symptoms off the medication can determine the need for further treatment. If the patient is monitored correctly, there should be more than enough time to begin the hormone therapy again if necessary.

Male patients who are unable to produce sex hormones will not be able to stop exogenous testosterone replacement therapy and this must continue indefinitely.

patients who are having trouble producing sex hormones, but whose levels are in an area that may enable them to actually produce sex hormones after levels are brought back to normal should begin a treatment cycle of 10-12 weeks and then cease the treatment for three weeks. patients should, after the third week, have a hormone level test re-administered, to determine if hormone production has regenerated. If not, then hormone replacement therapy should begin again.

If the patient is monitored correctly, there should be more than enough time to begin the hormone therapy again if necessary. The patient should be monitored for hypogonadism and have a lean body mass assessment taken once a month.

When to Begin Treatment Again
If the patient shows signs and symptoms of new hypogonadism or is experiencing an unexplained reduction in lean muscle tissue, then it is appropriate to begin the hormone therapy again.

Conclusion
Hormone therapies, which include anabolic steroids, appear to be some of the most effective and least expensive therapies for wasting syndrome. Hormone replacement therapy is the only effective treatment for a precursor to wasting, hypogonadism. Because of the intensely negative atmosphere surrounding anabolic steroids and Congress, passage of the Anabolic Steroid Control Act of 1990, physicians continue to refuse their patients access to hormone therapies, regardless of their proven effectiveness in the treatment of HIV/AIDS.

The end result is that people with HIV/AIDS are continuing to suffer from wasting unnecessarily. Others, out of desperation, are forced to enter the dangerous anabolic steroid black market to receive medications for therapy.

In 1993, Scott Lukas, chair of the American Society for Pharmacology and Experimental Therapeutics Committee on Substance Abuse, advocated continued research of the effectiveness, toxicity and natural history of anabolic-androgenic steroids.⁹⁸ In order to determine the overall effectiveness of hormone therapies in the treatment of HIV/AIDS, cancer and multiple sclerosis, more formal scientific studies need to be conducted. Many experts agree that to fully understand future applications of hormone therapies, patients, healthcare professionals and activists must apply pressure to the National Institutes of Health and other federal institutions to unequivocally call for more studies of these life-saving medications.<\p>

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