GMHC Treatment Issues 1994 Sep 1; 8(8): 2
HIV-associated weight loss, or wasting syndrome, is a major
cause of illness and death in patients with late-stage HIV
infection. It can be divided into two categories: acute weight
loss, which often rebounds after an opportunistic infection is
brought under control, and chronic weight loss, which is more
difficult to reverse. Either decreased nutrient intake or
alterations in metabolism can lead to weight loss. These
factors can arise directly from HIV infection as well as from
opportunistic infections, cancers or pre-existing
It is important to differentiate between mere loss in weight
and the loss of protein stores (in lean tissue) that occurs
during HIV infection. When acute weight loss is halted by
treating an opportunistic infection, an individual may regain
lost weight by adding fat rather than rebuilding lean tissue.
Simply taking in more nutrients does not automatically produce
recovery from wasting. AIDS-related wasting differs
qualitatively from starvation. In starvation, the body's
protein stores and muscle mass is conserved while basic
metabolic rates slow and fat deposits are broken down for
energy. During AIDS, the reverse happens. Studies by Kotler and
others meanwhile indicate that death from wasting is related to
the loss of lean body mass rather than just the amount of
Alterations in Metabolism
Primary infection with HIV or secondary opportunistic
infections changes the body's metabolic pathways. Abnormal
patterns of protein and lipid metabolism result, with nutrients
transferred from lean to adipose (fat) tissue. Some
inflammatory cytokines (intercellular immune regulators), such
as tumor necrosis factor (TNF) and interleukin-1, have been
associated with metabolic dysregulation and wasting. Their
chronic release during HIV infection seems to play a major role
in HIV-related wasting. Endocrine abnormalities, including
changes in gonadal, adrenal and thyroid function, have been
noted in HIV-infected individuals and are another possible
cause of weight loss and wasting.[3,4] One recent paper
reported that people with AIDS-related wasting syndrome had
significantly less testosterone and more prolactin and cortisol
than similar people without wasting. Testosterone promotes
the growth and maintenance of muscle tissue. The decrease in
testosterone may be related to the increased prolactin.
Cortisol is an adrenal hormone that modulates stress. One of
its functions is to free existing protein stores to repair
tissue damage elsewhere in the body. Finally, progressive
muscle weakness (myopathy), is an ill-defined condition that
may be caused by HIV itself or extended use of AZT. It is
reversible in the latter case.
Approved Treatments for Wasting
Two appetite stimulants are the only FDA-approved therapies
specifically for AIDS-related wasting syndrome.
Dronabinol (Marinol) is the psychoactive component of
marijuana. In trials, dronabinol improved appetite and weight
gain (mostly body fat) in about half of the participants. Side
effects associated with Dronabinol include dizziness, thinking
abnormalities, asthenia (weakness or loss of strength) and
Megestrol acetate (Megace) is a synthetic progesterone (steroid
hormone) in oral suspension. A twelve-week, placebo-controlled
study conducted in patients with AIDS-related wasting provided
the basis for its approval. Weight gains of five to seven
pounds were observed in the megestrol acetate group, and
two-pound losses were observed in the placebo group. Phase
II studies are underway to evaluate the combination of Marinol
Side effects of Megace include high blood pressure, leg
swelling, diabetes and impotence. (In addition, there was a
trend toward a higher death rate in one study's treatment arm.)
Megace, like Marinol, is widely considered to increase weight
without adding to lean body mass (see article on the Tenth
International Conference on AIDS). Appetite stimulants alone
may not be able to overcome the basic metabolic changes wrought
by the chronic response to HIV and the concurrent opportunistic
infections. Reversing wasting may require "anabolic" agents
that, like testosterone, promote muscle formation and
discourage fat buildup.
Human Growth Hormone
Recombinant human growth hormone (rHGH) and insulin-like growth
factor (IGF-1) are two growth stimulators currently under study
as therapies for wasting.
rHGH is a synthetic version of pituitary gland-derived human
growth hormone. It is made by genetic engineering and used for
the treatment of dwarfism. rHGH can induce positive nitrogen
balance, promote protein sparing and increase weight gain and
lean body mass in patients with AIDS-related wasting. Side
effects of rHGH include joint aches, fevers and high blood
Two preliminary studies published last year found that human
growth hormone triggered significant weight gain in people with
HIV wasting.[8,9] See the box on the International Conference
on AIDS for the first analysis of a much larger, more extended
trial of rHGH. The presentation on this trial was very
IGF-1 is produced by the liver in response to human growth
hormone. Many, but not all, of growth hormone's effects seem to
really be the result of IGF-1. A trial comparing growth hormone
and insulin-like growth factor is being conducted at the
National Cancer Institute, but a trial examining the
combination of the two yielded negative results (see below).
Testosterone and the chemically similar synthetic anabolic
steroids have been used by athletes and body builders to
increase their muscle mass and stamina. Anabolic steroids can
be dangerous, though, and medical supervision is desirable.
Community doctors have found that testosterone replacement
therapy can improve patients' mood, sexual function, appetite
and energy, although the long-term effects on immune function
are not known. Testosterone replacement is generally not
sufficient to manage weight loss and increasing testosterone
levels to above normal can have adverse effects, including
liver damage. A limited number of studies indicates that some
of the newer synthetic oral testosterone derivatives have fewer
side effects, and anecdotal reports claim that they increase
immune cell populations (CD8 and CD4). Dr. Kotler, at St.
Luke's/Roosevelt Hospital in New York, is conducting trials
with oral oxandrolone, a synthetic anabolic. Early results
indicate that patients taking oxandrolone experience weight
gain. Upon termination of treatment, weight loss resumed,
however. There was no evidence of CD8 or CD4 cell increases
resulting from oxandrolone therapy. During short-term use, no
overt side effects were noted but studies examining long- term
use have not been done. The effects of anabolic steroids on
women in particular need further monitoring, although
oxandrolone is reputed to have few masculinizing effects.
Anabolic steroids such as deca-durabolin have become popular as
an underground therapy among people with AIDS. Many feel that
these compounds work much better when accompanied by a rigorous
exercise program. Future studies should be conducted to
evaluate the combination of anabolic steroids with growth
hormone and testosterone replacement. The ideal therapy may
well be an individualized one that includes hormone- and
cytokine-modulating agents as needed but starts with such
simple supportive measures as exercise and food supplements.
Pentoxifylline is a medication for blood circulation disorders.
It also inhibits the activity of TNF and might in this way help
reverse wasting syndrome. An NIH-sponsored study has found that
after eight weeks on pentoxifylline, triglycerides (lipids) in
blood serum dropped significantly and TNF production went
down. Researchers at the Veterans Affairs Hospital in
Brooklyn, New York studied the drug's effect on wasting
syndrome in patients with AIDS but were not able to detect any
weight gain or reversal of wasting. Another recent study
found that pentoxifylline at a dose of 800 mg three times daily
did not affect the T-cell counts, viral load or TNF in eight
patients treated for three weeks.
Thalidomide is enjoying a revival as a TNF blocker. Recently,
two separate studies, one in France and another at Rockefeller
University in New York City, have shown significant weight gain
in patients receiving thalidomide. Thalidomide's abilities in
this area are now the subject of further study. For the latest
results, see the article on the AIDS Conference.
OP-1, a mixture of polypeptides, glycopeptides and glycosides,
is another reputed TNF inhibitor. Its developer, Omega
Pharmaceuticals, is just now beginning clinical trials of OP-1
for AIDS-related wasting.
Cells in the GI tract are particularly prone to damage during
HIV infection, and this results in reduced absorption of
nutrients. The HIV virus itself, intestinal parasites, and
colitis induced by cytomegalovirus (CMV) are the main sources
of tissue damage. The diarrhea connected with these conditions
also may result in malabsorption. Fat, carbohydrate, protein
and micronutrient (vitamin and mineral) malabsorption can
occur. Malabsorption may also be a condition that pre-exists
infection with HIV.
Infection by intestinal parasites triggers diarrhea and
malabsorption in persons with AIDS by causing atrophy of the
villi - the small threadlike projections on the interior of the
small intestines which absorb nutrients when working properly.
Given the variety of intestinal parasites, electron microscopic
analysis of intestinal biopsy is required for a conclusive
diagnosis. This procedure is both uncomfortable and expensive.
It is also difficult to perform and may be unavailable in many
The protozoa Cryptosporidium parvum, the most commonly
identified parasite in people with AIDS, causes massive
secretory diarrhea. Paramomycin (Humatin) at 500 mg four times
a day has demonstrated positive results in some patients
although relapse is common after the drug is discontinued.
For persons with a more mild infection, a lactose-free, low-fat
diet with a high calorie, protein-rich fluid supplementation is
helpful. The large amounts of sugars or long-chain proteins
found in some nutritional drinks tend to engender bloating and
heightened diarrhea. Persons with severe untreatable diarrhea
may also require parenteral (intravenous) fluid administration
to maintain a normal state of hydration and electrolyte
Among the drugs under investigation for cryptosporidiosis is
intravenous azithromycin. This formulation of the drug is
available directly from the manufacturer, Pfizer, on a
compassionate use basis (call 800/742-3029 for further
information). Side effects of IV azithromycin include nausea
and abdominal pain. Oral azithromycin failed to show an effect
on the frequency of bowel movements, parasite shedding in the
stool or overall clinical response in a placebo-controlled
study of 90 patients with cryptosporidiosis conducted at
Cornell Medical Center.
Another anti-crypto agent in development consists of
concentrated antibodies derived from cow's milk. Bioimmune
Systems of Salt Lake City is just beginning preliminary human
trials in HIV-negative individuals of its oral, milk-derived
antibody product, known as Immuno-C. An efficacy trial for 40
people with AIDS-related cryptosporidiosis is expected later in
the fall and will include six to eight sites around the
country. More information may be obtained by calling Joy
Erickson of Bioimmune Systems at 801/582-2345.
A second cow's milk preparation is called CryptoGAM. It is
manufactured by Immucell and licensed by Univax. CryptoGAM
failed as an oral agent in several early trials apparently
because it was broken down in the stomach before it reached the
intestines. A new open label trial is currently being conducted
by Louis Fries, M.D., from Univax. Very high dose CryptoGAM (40
grams per day) is introduced directly into the duodenum via a
nasogastric tube. Patients interested in the trial can contact
Dr. Fries at 301/770- 3099.
Microsporidia (Enterocytozoon bieneusi or Septata intestinalis)
is a second common GI parasite in people with AIDS. Infection
can cause diarrhea and decreased intestinal absorption. The
drug albendazole has shown some promise and is currently the
subject of an NIH- sponsored trial. A preliminary report on
eight patients from Dr. Dominique Anwar of Grady Memorial
Hospital in Atlanta indicates that atovaquone (an approved
treatment for pneumocystis pneumonia) may be effective in
As a preventive measure, HIV-infected people with low CD4
counts should be extremely careful about the water they
consume. There are only three acceptable forms: distilled,
deionized or boiled. Water filters, standing water (wells), spa
waters and bottled spring water can be contaminated with
intestinal parasites. Ice cubes and soda fountain-type drinks
which mix tap water with syrup can also be contaminated. Use
distilled, deionized or boiled water in all foods that will not
be cooked and require water for their preparation. Because even
the smallest amount of contaminated water can cause infection,
fruits and vegetables rinsed with tap water could be a source
Nutritional support is very important for individuals with HIV
infection. Anabolic drugs will have little effect without
sufficient diet. Studies also indicate that diets high in
protein and complex carbohydrates, moderate in fats and sugars
are important for good immune function.
Use of nutritional drinks such as Nutren, Ensure Plus, and
Sustacal can increase caloric intake for individuals who are
having trouble consuming enough calories. Because both
individuals' needs and the products' compositions vary, one
supplement may be better suited than another for a particular
situation. Patients should consult their physicians or a
nutritional counselor before adding nutritional drinks to their
diets. Little data from controlled trials exist, though, so it
is difficult to assess the actual benefit of supplementation.
Lipisorb is a food supplement containing medium chain
triglycerides that may benefit patients with fat malabsorption.
Elemental (predigested) diets are comparatively easy to absorb
in the GI tract and reportedly have helped lessen diarrhea and
stabilize weight. In patients unable to eat, data from two
studies suggest that enteral gastrostomy feeding (feeding
through a tube placed directly into the stomach through the
skin) can result in weight gain and increased lean body
Total parenteral nutrition (TPN) is a form of liquid nutrition
infused directly into the bloodstream. Studies indicate that
patients receiving TPN gain significant amounts of body cell
mass and weight if they are free of systemic infections. Other
studies have shown that administering TPN during secondary
infection can increase weight gain and improve the quality of
life by improving the individual's ability to fight
infection. Investigators also have reported that TPN has
favorable effects on immune cell responsiveness. But TPN
can cost up to $13,000 a month in a home care environment. It
is usually used to support someone through a limited period of
acute illness but may be required for more lengthy periods.
Exercise can promote protein formation in tissues throughout
the body. It is a helpful therapy when physical health permits.
To build up lean body mass, resistance exercises (such as
weight lifting) are more important than aerobic exercises,
although aerobic exercise can also be beneficial. Exercise
promotes muscle formation by increasing the number of
testosterone receptors. Proper timing of food intake is also
important in weight lifting. It is a good idea to eat well but
not immediately prior to lifting weights and to eat a high
protein food one to two hours after lifting.
A variety of therapeutic strategies are available for different
aspects of HIV-associated wasting. There is a strong
correlation between proper weight, good nutritional status and
survival. Individuals should chart their weight, noting any
significant change, and physicians should take determined steps
to diagnose and treat major weight loss. Correct diagnosis and
aggressive treatment can improve quality of life and prolong
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3 Jones PD et al. Journal of Acquired Immune Deficiency
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4 Landman A et al. Thirty-second Interscience Conference on
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5 Coodley GO et al. Journal of Acquired Immune Deficiency
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