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Anorexia/Cachexia in Patients with HIV: Lessons for the Oncologist

Anorexia/Cachexia in Patients with HIV: Lessons for the Oncologist

ABSTRACT: Early intervention and attention to nutritional status are essential in patients with cachexia. Identification of reversible causes of decreased energy intake and/or weight loss is the first step in treatment. When such factors cannot be identified, pharmacologic interventions should be considered. To date, megestrol acetate is the most effective appetite stimulant. Appetite and weight gain occur to a greater and more rapid degree as megestrol dose increases. Unfortunately, the weight gain is due predominantly to an increase in fat mass. Whether this is due to a lack of exercise in the face of increased caloric intake and/or to the hypogonadal effects of megestrol acetate is being tested in ongoing clinical trials. Anabolic agents, particularly growth hormone, are exciting potential therapies. No data are yet available on alternate doses and schedules of growth hormone or on its effect in patients with decreased oral intake. Current studies addressing combination therapy with anabolic agents and appetite stimulants should clarify their respective therapeutic roles. [ONCOLOGY 10(7):1049-1056, 1996]


Anorexia and cachexia are frequent complications of both HIV infection
and cancer. Involuntary weight loss and associated malnutrition
result in physical and psychological consequences that affect
both morbidity and mortality. Numerous investigators have reported
on the relationship between involuntary weight loss and adverse
outcome in the setting of HIV infection or cancer. Malnutrition
adversely affects immune function, increases the risk of infection,
and diminishes tolerance to radiation therapy, response to chemotherapy,
and overall survival [1].

Whether nutritional status is evaluated using simple clinical
nutritional markers, such as serum albumin and percentage of usual
body weight, or by sophisticated research techniques, the deleterious
effects of malnutrition on the clinical course of HIV infection
are well documented. Indeed, malnutrition is a predictor of both
risk of hospitalization and survival [2]. Regardless of the clinical
setting, death from wasting is directly related to the magnitude
of tissue depletion, suggesting that the preservation and/or restoration
of body cell mass may enhance survival [3].

Pathogenesis of Wasting

The pathogenesis of wasting is incompletely defined. However,
it appears to result from complex interactions among decreased
energy intake, altered energy expenditure, malabsorption, and
hormonal/cytokine and metabolic abnormalities. The respective
roles of individual factors, such as altered insulin sensitivity,
hypertriglyceridemia, futile cycling of glucose and/or free fatty
acids, hypermetabolism or hypometabolism, and alterations in the
cytokine milieu, are difficult to identify. Ultimately, weight
loss is determined by the balance between energy intake and energy
expenditure. Increasingly, data suggest reduced energy intake
as the major determinant of involuntary weight loss in patients
with HIV infection, and, to a less degree, in those with cancer

Anorexia is a frequent clinical complaint of patients with malignant
disease or HIV infection. Bruera, in a review of 275 consecutive
cancer patients admitted to a palliative care unit, noted anorexia
to be present in 85% of patients, second in frequency only to
the complaint of asthenia and more common than complaints of cancer-related
pain [1].

Similarly, anorexia is a highly prevalent symptom in the setting
of HIV infection, although its exact prevalence is unknown. In
a review of clinical risk factors for malnutrition in 104 HIV-infected
patients (including asymptomatic patients, as well as those with
AIDS or AIDS-related complex [ARC]), anorexia was identified as
the predominant risk factor in 60% of patients [6]. Furthermore,
Burger et al reported the benefit of intensified oral nutritional
intervention in malnourished HIV-infected outpatients, suggesting
that poor spontaneous nutrient intake is an important pathogenetic
factor in the development of HIV-related malnutrition [7].

In patients with HIV infection, the degree of weight loss has
been closely associated with reduced energy intake. McCorkindale
et al noted a correlation between weight loss and decreased oral
intake over a 16-month period in asymptomatic patients with HIV
infection or early ARC [8]. In an evaluation by Grunfeld et al
comparing metabolic parameters and oral intake in HIV-seropositive
subjects, seronegative controls, and AIDS patients with and without
active secondary infections, a highly significant correlation
between 28-day weight loss and caloric intake was identified,
while no correlation was seen between resting energy expenditure
and weight loss [5]. Similarly, Macallan et al found reduced energy
intake, not elevated energy expenditure, to be the primary determinant
of weight loss in 27 HIV-seropositive men at different stages
of the disease [4].

Although weight loss appears to be progressive over the course
of HIV infection, it does not occur continuously. Rather, weight
is more often lost in a stepwise fashion in association with opportunistic
complications of the underlying immunosuppression. This episodic
weight loss is associated with decreased oral intake, which, during
its early stages, may be amenable to therapeutic intervention.

Although not all investigators agree, a number of studies suggest
that attention to oral intake by clinicians results in an improvement
in overall nutritional status. McKinley et al demonstrated improved
nutritional status in adult outpatients who received nutritional
assessment, counseling, and follow-up, compared with outpatients
who received no nutritional intervention [9]. In contrast, Chleblowski
et al reported progressive weight loss in HIV-infected individuals
despite dietary counseling, suggesting the need for earlier intervention
and consideration of increased target levels for energy intake

Etiology of Anorexia

The etiology of anorexia is incompletely understood.

Cytokine Production

The endogenous production of cytokines contributes to the development
of anorexia and cachexia in both HIV infection and advanced cancer.
Experimental therapy in vitro and in vivo with cytokines, such
as interferon, tumor necrosis factor (TNF), and interleukin-1
(IL-1), can produce striking anorexia [11-13]. Tumor necrosis
factor, although frequently cited as a major cause of anorexia,
is not consistently elevated in the serum of patients with cancer
cachexia or HIV-related wasting [11-14].

Although individual cytokines can result in significant anorexia
when given as single factors in the experimental setting, tolerance
to their anorexic effects generally develops and normal food intake
resumes [11]. Synergism between cytokines (eg, IL-1 plus interferon-alfa
or TNF) may result in irreversible anorexia, metabolic abnormalities,
and progressive weight loss.

Reversible Causes

Food intake may be further decreased by readily identifiable,
often reversible causes.

Nausea and Vomiting--Chronic nausea is a frequent complaint
in patients with HIV infection or cancer. Nausea and vomiting
can occur as a result of mechanical obstruction, infectious complications,
or as a side effect of medications (see Tables 1 and 2).

In the setting of HIV infection, numerous medications are prescribed
both for prophylaxis and treatment of opportunistic infections
that, alone or in combination, may cause nausea and vomiting;
examples include sulfamethoxazole for the treatment of Pneumocystis
pneumonia or clarithromycin (Biaxin) as therapy or
prophylaxis for Mycobacterium avium complex.

Nausea and vomiting occur as both an immediate and late effect
of treatment with chemotherapeutic drugs such as cisplatin (Platinol).
Radiation therapy, particularly when the treatment field includes
the gastrointestinal tract, may also cause significant nausea.

In patients with advanced disease, whether cancer or HIV infection,
a not infrequent cause of nausea and vomiting is a rapid increase
in the dose of narcotic analgesics. In patients receiving high
doses of narcotics, nausea may be severe, chronic, and accompanied
by other gastrointestinal symptoms, including abdominal pain,
constipation, and large bowel distention.

Psychosocial or Financial Factors--Decreased oral intake
may result from psychosocial or financial factors. Patients have
identified anxiety, depression, and/or a sense of isolation as
factors interfering with oral intake. Neuropsychiatric symptoms
associated with HIV infection and opportunistic pathogens of the
central nervous system or central nervous system metastases, including
dementia, sensory and motor abnormalities, and psychosis, also
may result in decreased caloric intake.

Mechanical impediments to food intake secondary to strictures
and/or progressive malignant disease further impair nutritional
status. Oral and esophageal conditions that result in dysphasia
and food aversions, such as esophageal candidiasis, aphthous stomatitis,
and therapy-induced mucositis, occur in patients with both cancer
and HIV infection. Cytomegaloviral or herpetic esophagitis are
most frequently seen in the severely immunocompromised host. Bulky
oropharyngeal Kaposi's sarcoma or other aerodigestive tract malignancies
may also make eating painful or unpleasant.

Early satiety may further compromise oral intake. Early
satiety may be secondary to ascites, hepatomegaly, or massive
splenomegaly (due to progressive malignancy or organ infiltration
by opportunistic infections [eg, cytomegalovirus or M avium
complex]). Abdominal fullness, regardless of the cause, has
been identified as one of the most important symptoms influencing
weight loss in patients with unresectable malignancy [15].

Diarrhea is the most common gastrointestinal tract symptom
in patients with HIV infection. It is often difficult to treat
and may become a major debilitating aspect of a patient's illness.
Not infrequently, diarrhea is associated with decreased oral intake,
perhaps because patients attempt to reduce fecal output by restricting
food intake, or because unabsorbed nutrients in the gastrointestinal
tract suppress appetite. Similarly, diarrhea is a prominent symptom
in patients with certain tumors, such as metastatic islet-cell


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