Evaluation and Treatment of Weight Loss in Adults with HIV Disease

Am Fam Physician. 1999 Sep 1;60(3):843-854.

  See related patient information handout on nutrition and exercise in patients with HIV, written by the authors of this article.

Weight loss late in the course of human immunodeficiency virus (HIV) disease is common and often multifactorial. Increased energy expenditure in response to opportunistic disease, as well as to HIV infection itself, can lead to protein–calorie malnutrition similar to that observed in starvation. Weight loss of as little as 5 percent in patients with HIV infection is associated with an increased risk of disease progression. Loss of body cell mass carries a particularly poor prognosis, and aggressive measures should be taken to stop such depletion. Patients exhibiting unexpected weight loss should be carefully examined to exclude decreased food intake, malabsorption, occult infection or neoplasm as the etiology of the weight loss. Early aggressive treatment of HIV disease and underlying opportunistic pathology, along with adequate pharmacologic, hormonal, nutritional and physical therapy, can often restore normal weight and body composition.

Wasting syndrome is included in the current case definition of acquired immunodeficiency syndrome (AIDS), as specified in 1993 by the Centers for Disease Control and Prevention (CDC). The CDC defines wasting syndrome as unexplained weight loss of more than 10 percent, accompanied by fever or diarrhea. The development of wasting syndrome is considered an indicator condition for AIDS.

Wasting syndrome in patients with human immunodeficiency virus (HIV) infection is a multifactorial process that can be associated with a variety of infectious, neoplastic, metabolic and nutritional abnormalities. Early identification and treatment can improve functional status and, perhaps, survival as well. Although not yet thoroughly studied with regard to HIV-related wasting, highly active antiretroviral therapy seems to have significantly reduced the prevalence of wasting syndrome among patients with HIV infection. Nonetheless, treatment failure despite intensive antiretroviral therapy is not uncommon, and HIV disease activity may place patients at risk for significant weight loss.

Pathogenesis

Profound weight loss commonly occurs late in the course of HIV disease and is associated with a poor prognosis, more rapid disease progression, significant disability and increased mortality. HIV-related wasting is a starvation state characterized by protein–energy malnutrition in which mobilization of fat is accompanied by loss of somatic and visceral proteins. Loss of more than 30 percent of ideal body weight is associated with high mortality,1 and weight loss of as little as 5 percent of the patient's usual weight is associated with more rapid progression of disease.2 Weight loss, however, is a relatively insensitive indicator of early wasting syndrome, and decreases in certain body compartments, particularly body cell mass, may portend early death if this depletion is not reversed.

Loss of body cell mass can result from a variety of causes but usually is a result of inadequate intake in the context of active opportunistic disease, HIV disease (as indicated by a high viral load), or both. Certain pro-inflammatory cytokines, particularly tumor necrosis factor-α (TNF-α), have also been implicated, although their precise roles in wasting syndrome are still unclear.

Plasma HIV RNA is an independent predictor of wasting,3 and effective suppression of HIV RNA with antiretroviral therapy may significantly forestall the onset of weight loss. The role of protease inhibitors in the pathogenesis of abnormalities in lipid metabolism and body composition is under study, but their effects may have implications for new forms of wasting.4,5

Identifying Contributing Factors

Evaluation of patients with wasting syndrome focuses on determining if active HIV disease is present and identifying systemic opportunistic infections and barriers to effective nutrition.

OTHER DISEASE

HIV infection and a variety of bacterial, mycobacterial, fungal, parasitic and other viral pathogens may result in profound weight loss. Plasma HIV RNA must be assessed, and HIV infection must be aggressively treated to bring the HIV RNA level to below the limits of detection, if possible. Opportunistic infections commonly associated with wasting syndrome include disseminated Mycobacterium avium complex infection, cytomegalovirus infection and Pneumocystis carinii pneumonia. Such opportunistic infections most often develop in patients with advanced disease. Tuberculosis may also be an important consideration, especially among inner-city residents, injection-drug users, the homeless and other high-risk groups. In addition, occult malignancy, particularly B-cell lymphoma, may present as wasting syndrome.

DRUG EFFECTS

Several medications commonly used in the treatment of HIV disease, especially antiretroviral agents, macrolide antibiotics and chemotherapy, may cause anorexia, nausea or vomiting. In addition, drug interactions can increase serum levels of offending medications, exacerbating the problem.

GASTROINTESTINAL DISORDERS

Tables 1 and 2 summarize gastrointestinal conditions that commonly interfere with nutritional intake in patients with HIV infection. Pain, impaired deglutition and early satiety related to upper gastrointestinal tract pathology may limit food intake.6 Other conditions not intrinsically related to HIV, such as dental caries, gallbladder disease, peptic or duodenal ulcerative disease and gastroesophageal reflux, may cause pain and limit food intake, thus contributing to the development of wasting syndrome. Interestingly, the frequency of Helicobacter pylori gastritis is not known to be increased in patients with HIV infection.

TABLE 1

CD4+ Counts and Common Gastrointestinal Conditions Contributing to HIV-Related Wasting

Site of disease Condition Clinical signs Treatment

CD4+ count <500 cells per mL

Oropharynx

Aphthous stomatitis

Ulcerations

Topical steroid, thalidomide (Thalomid)

Gingivitis, periodontitis

Bleeding, necrosis

Debridement; povidone/iodine and chlorhexidine, with or without an antibiotic

Xerostomia

Dry mucosa

Saliva substitute

Drug-associated xerostomia

Ulcerations, dry mucosa

Change therapy

HSV infection

Vesicles, ulcerations

Acyclovir (Zovirax)

Candidal infection

White plaques, erythema

Antifungal agent

Esophagus

Candidal infection

Erosion, exudate

Antifungal agent

HSV infection

Ulceration

Acyclovir

Small intestine

Lactose intolerance

Diarrhea

Diet modification, enzyme replacement

Giardia lamblia infection

Diarrhea

Metronidazole (Flagyl)

Viral enteritis

Diarrhea

Symptomatic treatment

Clostridium difficile infection

Diarrhea

Metronidazole

Colorectum

HSV infection

Ulceration, fissure

Acyclovir

CD4+ count <200 cells per mL

Small intestine

Cryptosporidiosis

Diarrhea

Symptomatic therapy

Microsporidiosis

Diarrhea

Albendazole (Albenza)

CD4+ count <50 cells per mL

Oropharynx

Kaposi's sarcoma

Mass, ulceration

Chemotherapy and/or radiation therapy

Lymphoma

Mass

Chemotherapy and/or radiation therapy

Esophagus

Cytomegalovirus infection

Ulceration

Ganciclovir (Cytovene), foscarnet (Foscavir) or cidofovir (Vistide)

Mycobacterium avium complex infection

Ulceration

A macrolide antibiotic (i.e., clarithromycin [Biaxin] or azithromycin [Zithromax]) and ethambutol (Myambutol), with or without rifabutin (Mycobutin)

Stomach

B-cell lymphoma

Mass

Chemotherapy and/or radiation therapy

Kaposi's sarcoma

Mass

Chemotherapy and/or radiation therapy

Small intestine

M. avium complex infection

Ulceration, granulation

A macrolide antibiotic (i.e., clarithromycin or azithromycin) and ethambutol, with or without rifabutin

B-cell lymphoma

Mass

Chemotherapy and/or radiation therapy

Kaposi's sarcoma

Mass

Chemotherapy and/or radiation therapy

Colorectum

M. avium complex infection

Ulceration, granuloma

A macrolide antibiotic (i.e., clarithromycin or azithromycin) and ethambutol, with or without rifabutin


HIV = human immunodeficiency virus; HSV = herpes simplex virus infection.

TABLE 1   CD4+ Counts and Common Gastrointestinal Conditions Contributing to HIV-Related Wasting

View Table

TABLE 1

CD4+ Counts and Common Gastrointestinal Conditions Contributing to HIV-Related Wasting

Site of disease Condition Clinical signs Treatment

CD4+ count <500 cells per mL

Oropharynx

Aphthous stomatitis

Ulcerations

Topical steroid, thalidomide (Thalomid)

Gingivitis, periodontitis

Bleeding, necrosis

Debridement; povidone/iodine and chlorhexidine, with or without an antibiotic

Xerostomia

Dry mucosa

Saliva substitute

Drug-associated xerostomia

Ulcerations, dry mucosa

Change therapy

HSV infection

Vesicles, ulcerations

Acyclovir (Zovirax)

Candidal infection

White plaques, erythema

Antifungal agent

Esophagus

Candidal infection

Erosion, exudate

Antifungal agent

HSV infection

Ulceration

Acyclovir

Small intestine

Lactose intolerance

Diarrhea

Diet modification, enzyme replacement

Giardia lamblia infection

Diarrhea

Metronidazole (Flagyl)

Viral enteritis

Diarrhea

Symptomatic treatment

Clostridium difficile infection

Diarrhea

Metronidazole

Colorectum

HSV infection

Ulceration, fissure

Acyclovir

CD4+ count <200 cells per mL

Small intestine

Cryptosporidiosis

Diarrhea

Symptomatic therapy

Microsporidiosis

Diarrhea

Albendazole (Albenza)

CD4+ count <50 cells per mL

Oropharynx

Kaposi's sarcoma

Mass, ulceration

Chemotherapy and/or radiation therapy

Lymphoma

Mass

Chemotherapy and/or radiation therapy

Esophagus

Cytomegalovirus infection

Ulceration

Ganciclovir (Cytovene), foscarnet (Foscavir) or cidofovir (Vistide)

Mycobacterium avium complex infection

Ulceration

A macrolide antibiotic (i.e., clarithromycin [Biaxin] or azithromycin [Zithromax]) and ethambutol (Myambutol), with or without rifabutin (Mycobutin)

Stomach

B-cell lymphoma

Mass

Chemotherapy and/or radiation therapy

Kaposi's sarcoma

Mass

Chemotherapy and/or radiation therapy

Small intestine

M. avium complex infection

Ulceration, granulation

A macrolide antibiotic (i.e., clarithromycin or azithromycin) and ethambutol, with or without rifabutin

B-cell lymphoma

Mass

Chemotherapy and/or radiation therapy

Kaposi's sarcoma

Mass

Chemotherapy and/or radiation therapy

Colorectum

M. avium complex infection

Ulceration, granuloma

A macrolide antibiotic (i.e., clarithromycin or azithromycin) and ethambutol, with or without rifabutin


HIV = human immunodeficiency virus; HSV = herpes simplex virus infection.

TABLE 2

Factors That May Affect Nutritional Intake in Patients with HIV Disease

Finding Cause Treatment

Constitutional

Anorexia

Opportunistic disease

Disease-specific therapy

HIV

Highly active antiretroviral therapy

Depression

Antidepressant

Dementia

Highly active antiretroviral therapy

Substance abuse

Specific therapy

Nausea

Medications

Assess drug interactions

Alternative therapies

Adjust therapy

Idiopathic

Antiemetics

Oropharynx

Xerostomia

Medications

Adjust therapy

HIV(?)

Hydration, lozenges, consider pilocarpine (Pilopine)

Odontogenic infection

Oral flora

Clindamycin (Cleocin), 300 mg every 6 hours; dental referral

Ulceration

Aphthous stomatitis

Thalidomide (Thalomid), 50 to 200 mg once daily; dexamethasone mouth rinse

HSV infection

Acyclovir (Zovirax), 400 mg 3 times daily

Erythema, exudate

Candidal infection

Clotrimazole (Mycelex) troches, 10 mg every 4 hours; fluconazole (Diflucan), 100 mg once daily (for resistant species only)

Mass

Kaposi's sarcoma

Chemotherapy and radiation therapy

Esophagus

Ulceration

Cytomegalovirus infection

Ganciclovir (Cytovene), 5 mg per kg IV twice daily for 2 weeks, then 1 g orally 3 times daily

HSV infection

Acyclovir, 400 mg 3 times daily

Mycobacterium avium complex infection

Clarithromycin (Biaxin), 500 mg 2 times daily, or azithromycin (Zithromax), 600 mg once daily, and ethambutol (Myambutol), 15 to 25 mg per kg per day, with or without ciprofloxacin (Cipro) or rifabutin (Mycobutin)

Ulceration/exudates

Candidal infection

Fluconazole, 100 to 200 mg once daily

Mass

Kaposi's sarcoma, B-cell lymphoma

Chemotherapy and/or radiation therapy

Abdominal pain

Pancreatitis

Medications

Adjust therapy

Cytomegalovirus infection

Ganciclovir, 5 mg per kg IV 2 times daily for 2 weeks, then 1 g orally 3 times daily


HIV = human immunodeficiency virus; HSV = herpes simplex virus; IV = intravenously.

TABLE 2   Factors That May Affect Nutritional Intake in Patients with HIV Disease

View Table

TABLE 2

Factors That May Affect Nutritional Intake in Patients with HIV Disease

Finding Cause Treatment

Constitutional

Anorexia

Opportunistic disease

Disease-specific therapy

HIV

Highly active antiretroviral therapy

Depression

Antidepressant

Dementia

Highly active antiretroviral therapy

Substance abuse

Specific therapy

Nausea

Medications

Assess drug interactions

Alternative therapies

Adjust therapy

Idiopathic

Antiemetics

Oropharynx

Xerostomia

Medications

Adjust therapy

HIV(?)

Hydration, lozenges, consider pilocarpine (Pilopine)

Odontogenic infection

Oral flora

Clindamycin (Cleocin), 300 mg every 6 hours; dental referral

Ulceration

Aphthous stomatitis

Thalidomide (Thalomid), 50 to 200 mg once daily; dexamethasone mouth rinse

HSV infection

Acyclovir (Zovirax), 400 mg 3 times daily

Erythema, exudate

Candidal infection

Clotrimazole (Mycelex) troches, 10 mg every 4 hours; fluconazole (Diflucan), 100 mg once daily (for resistant species only)

Mass

Kaposi's sarcoma

Chemotherapy and radiation therapy

Esophagus

Ulceration

Cytomegalovirus infection

Ganciclovir (Cytovene), 5 mg per kg IV twice daily for 2 weeks, then 1 g orally 3 times daily

HSV infection

Acyclovir, 400 mg 3 times daily

Mycobacterium avium complex infection

Clarithromycin (Biaxin), 500 mg 2 times daily, or azithromycin (Zithromax), 600 mg once daily, and ethambutol (Myambutol), 15 to 25 mg per kg per day, with or without ciprofloxacin (Cipro) or rifabutin (Mycobutin)

Ulceration/exudates

Candidal infection

Fluconazole, 100 to 200 mg once daily

Mass

Kaposi's sarcoma, B-cell lymphoma

Chemotherapy and/or radiation therapy

Abdominal pain

Pancreatitis

Medications

Adjust therapy

Cytomegalovirus infection

Ganciclovir, 5 mg per kg IV 2 times daily for 2 weeks, then 1 g orally 3 times daily


HIV = human immunodeficiency virus; HSV = herpes simplex virus; IV = intravenously.

Diarrheal diseases often occur throughout HIV disease. Lactose intolerance is quite common and should be considered in the differential diagnosis. Enteric viruses are present in over 50 percent of seropositive patients who have diarrhea and in whom no other pathogens can be identified.7 Bacterial and parasitic enterocolitis can also be a problem, especially if the CD4+ cell count is low. Notably, Clostridium difficile may cause symptomatic infection even in the absence of antibiotic therapy.

PSYCHIATRIC DISORDERS

Depression, dementia and substance abuse are also associated with decreased intake and should be considered in the differential diagnosis of wasting syndrome.

History

MEDICAL

Information about previous opportunistic infections should be obtained. A list of current medications, including alternative therapies, should be reviewed at each visit, along with the possibility of side effects from any of the agents the patient is receiving.

The review of systems should focus on the presence of symptoms that suggest opportunistic disease, decreased intake or malabsorption as the etiology of wasting syndrome. Fever, night sweats, fatigue, diarrhea, nausea, vomiting, difficulty swallowing, dyspnea or changes in mental status may indicate occult systemic infection or malignancy. Mood and cognition in all patients should be evaluated for signs of depression or dementia; referral for neuropsychologic testing may be required to define whether such signs represent depression or dementia.

NUTRITIONAL

A nutritional history, including the type and quantity of food, is essential in the evaluation of wasting syndrome. If available, consultation with a registered dietitian should be arranged to assess caloric, protein and micronutrient intake. This assessment can be accomplished with a 24-hour dietary recall or a dietary log. Assessment of dietary intake may uncover an eating disorder or the anatomic location of opportunistic disease, and it also may suggest a means of improving nutritional intake.

ACTIVITY LEVEL

The level of physical activity, especially that related to muscle building, should be assessed. Although standard survey instruments can be used, their utility in patients with HIV disease has not been validated. Alternatively, activity level can be assessed on the basis of the frequency, intensity, duration and type of exercise (Table 3). Although this approach has not been evaluated in the context of HIV disease, it has the virtue of simplicity and is based on American College of Sports Medicine recommendations.8 Referral to a physical therapist or an exercise physiologist will provide a more detailed, comprehensive assessment and plan.

TABLE 3

Designing an Exercise Regimen for Patients with HIV Disease

1. Assess the patient's current level of exercise, according to the guidelines below. Determine the patient's score for the frequency, intensity, duration and type of exercise.

Low (score 1)

Medium (score 2)

High (score 3)

Score


Frequency (days per week)

0 to 1

2 to 4

5 to 7

______

Intensity (percentage of capacity or strength)

40 to 55%

56 to 75%

>75%

______

Time (minutes per day)

10 to 25

26 to 55

56 to 90

______

Type of exercise

Aerobic

Walking, slow bicycling, etc.

Fast walking, jogging, mountain biking, etc.

Running, cross-country skiing, etc.

______

Resistance

Light weights

Circuit weights

Body building

______

2. Determine the patient's activity level based on the total score derived from the above information about quantity and quality of exercise.

Activity level

Low

Medium

High


Total score

<5

6 to 10

11 to 15

3. Recommend to the patient the following guidelines:

Begin exercise at the level indicated by the assessment score.

Gradually increase the amount of exercise as follows:

Week

Parameter


1

Increase the frequency by one day at the end of week 1 and maintain this frequency for two weeks.

3

Increase the intensity by no more than 10% at the end of week 3 and maintain this intensity for two weeks.

5

Increase the duration of each session by 5 minutes at the end of week 5 and maintain this duration for two weeks.

7 to 12

7 to 12 Maintain the increases in frequency intensity and duration made during the previous six weeks.

  • Once the highest score within any variable (frequency, intensity and duration) is reached, progress to the next level.

  • Exercise regimens should include 24 to 48 hours of rest between workout sessions to avoid injury and overtraining.

  • Be conservative about progressing the level of exercises. If necessary, progress every three to four weeks instead of every two weeks.

  • Do not work out during an acute illness. Following prolonged illness, begin workouts at a lower level of frequency, intensity and duration.

TABLE 3   Designing an Exercise Regimen for Patients with HIV Disease

View Table

TABLE 3

Designing an Exercise Regimen for Patients with HIV Disease

1. Assess the patient's current level of exercise, according to the guidelines below. Determine the patient's score for the frequency, intensity, duration and type of exercise.

Low (score 1)

Medium (score 2)

High (score 3)

Score


Frequency (days per week)

0 to 1

2 to 4

5 to 7

______

Intensity (percentage of capacity or strength)

40 to 55%

56 to 75%

>75%

______

Time (minutes per day)

10 to 25

26 to 55

56 to 90

______

Type of exercise

Aerobic

Walking, slow bicycling, etc.

Fast walking, jogging, mountain biking, etc.

Running, cross-country skiing, etc.

______

Resistance

Light weights

Circuit weights

Body building

______

2. Determine the patient's activity level based on the total score derived from the above information about quantity and quality of exercise.

Activity level

Low

Medium

High


Total score

<5

6 to 10

11 to 15

3. Recommend to the patient the following guidelines:

Begin exercise at the level indicated by the assessment score.

Gradually increase the amount of exercise as follows:

Week

Parameter


1

Increase the frequency by one day at the end of week 1 and maintain this frequency for two weeks.

3

Increase the intensity by no more than 10% at the end of week 3 and maintain this intensity for two weeks.

5

Increase the duration of each session by 5 minutes at the end of week 5 and maintain this duration for two weeks.

7 to 12

7 to 12 Maintain the increases in frequency intensity and duration made during the previous six weeks.

  • Once the highest score within any variable (frequency, intensity and duration) is reached, progress to the next level.

  • Exercise regimens should include 24 to 48 hours of rest between workout sessions to avoid injury and overtraining.

  • Be conservative about progressing the level of exercises. If necessary, progress every three to four weeks instead of every two weeks.

  • Do not work out during an acute illness. Following prolonged illness, begin workouts at a lower level of frequency, intensity and duration.

Physical Examination

The patient's body weight should be tracked in a standardized fashion. A flow sheet correlating the patient's weight, CD4+ cell count, HIV RNA level and other relevant laboratory results can be useful in detecting early signs of wasting syndrome. While the patient's weight can be compared with his or her ideal body weight, the utility of such a comparison in HIV-positive patients is not clear. The cause of any weight loss trend should be investigated, since early wasting may be present without a significant decrease in body weight. Body mass index (kg per m2) can be used to adjust for body habitus but is relatively insensitive to small changes in weight.

Routine physical examination of all HIV patients should focus on changes in body habitus and signs of opportunistic disease. Fragility of hair, skin texture and nail structure is a sign of inadequate protein intake. Central obesity, the presence of a dorsocervical fat pad (“buffalo hump”) and wasting of the extremities are associated with protease inhibitor therapy.

A comprehensive examination of the mouth to identify abnormalities that are impeding nutritional intake is essential. Dental caries, gingivitis and periodontitis are common in patients with HIV disease and should be treated. The oral mucosa should be inspected for erythema, exudates, ulcerations or masses suggestive of opportunistic disease. Edentulous patients should be examined after their dentures have been removed, if possible. Fungal cultures are usually unnecessary in cases of suspected candidiasis, and presumptive therapy can be safely given. Oral hairy leukoplakia, a common benign condition associated with Epstein-Barr virus infection, presents as striated white exudates adherent to the lingual margins; it usually requires no treatment.

The etiology of odynophagia or dysphagia should be evaluated. A barium esophagogram is a relatively sensitive means of detecting esophageal masses, ulcerations and dysmotility. Radiographic abnormalities should be endoscopically evaluated, with biopsy and cultures obtained as indicated.

Microscopic examination and culture of the stool may be warranted to exclude the presence of opportunistic pathogens in patients with diarrhea. Barium radiography of the upper and lower gastrointestinal tract may be useful for identifying obstruction or ulceration as the cause of the patient's symptoms. If colonic disease is suspected, however, lower endoscopy, with or without biopsy, is usually indicated. The anorectal area should be examined to identify any signs of systemic disease or causes of painful defecation.

Hypogonadism, including testicular atrophy, is common in men with HIV disease, and signs of hypogonadism should be looked for during physical examination. Although loss of secondary sex characteristics does not usually occur with hypogonadism, significant loss of lean body mass may be noted, since endogenous testosterone production is inadequate to maintain premorbid body cell mass.

Laboratory Studies

Laboratory assessment should initially be directed at identification of any underlying opportunistic pathology. Depending on the patient's symptoms, CD4+ count, blood cultures, chest radiography and oximetry, gastrointestinal biopsies or stool cultures may be indicated in addition to standard hematologic and chemistry tests.

Evaluation of protein synthesis (prealbumin and albumin levels), hormonal status (serum testosterone and thyroid profile) and micronutrient status (serum folate and vitamin B12) may be useful in conjunction with nutritional assessment and intervention. Lipid status should be ascertained by means of a fasting lipid profile as well, especially in patients receiving protease inhibitors.

Liver function tests should be performed regularly in patients who are taking anabolic steroids to curb wasting syndrome. Anabolic steroids have the potential for causing hepatotoxicity, especially in the context of HIV disease, when other medications and opportunistic infections may adversely affect hepatic function as well.

Regular monitoring of serum testosterone levels may be required in hypogonadal patients to ensure that hormonal replacement is adequate. Notably, endogenous testosterone production may decline with exogenous supplementation.

Because body cell mass may be lost before total body weight declines and because loss of body cell mass is predictive of a poor outcome, its assessment can be important, especially in patients with subclinical disease. Simple methods of measurement, such as determining the mid-arm circumference, are inexpensive and relatively accurate,9 although special training is required, and variability in measurements may be significant.

Bioelectrical impedance analysis (often referred to as “BIA”) is an accurate method of estimating body cell mass. Instruments for reliable measurements of body composition are commercially available (i.e., BIA Quantum; RJL Systems, Inc., Detroit). These devices can be used quickly in the office (Figure 1); a minimum of staff training is required. Bioelectrical impedance analysis provides an estimate of the total body water by measuring changes in a low electrical current passed between electrodes placed on the upper and lower extremities. The sizes of other body compartments (including body cell mass) are then calculated using equations based on assumptions about the relationships between different body compartments and total body water. The validity and reliability of the results depend heavily on several factors, including correct placement of the electrodes, “normality” of body habitus, hydration status and the equations used to estimate body cell mass.10

FIGURE 1.

Administration of bioelectric impedance analysis in the physician's office.

View Large


FIGURE 1.

Administration of bioelectric impedance analysis in the physician's office.


FIGURE 1.

Administration of bioelectric impedance analysis in the physician's office.

Treatment

Figure 2 gives an overview of important considerations in the management of HIV-positive patients who have weight loss. Treatment of wasting syndrome includes medical intervention, correction of dental problems and implementation of nutritional support, as well as patient education regarding the importance of exercise and the need to adhere to a highly active antiretroviral regimen. Alleviation of nausea, anorexia and pain is crucial to improving the patient's nutritional intake.

Evaluation and Treatment of Weight Loss in HIV Disease

FIGURE 2.

Algorithm for the evaluation and treatment of weight loss in patients with HIV disease. (CNS = central nervous system; HIV = human immunodeficiency virus; UGI = upper gastrointestinal)

View Large

Evaluation and Treatment of Weight Loss in HIV Disease


FIGURE 2.

Algorithm for the evaluation and treatment of weight loss in patients with HIV disease. (CNS = central nervous system; HIV = human immunodeficiency virus; UGI = upper gastrointestinal)

Evaluation and Treatment of Weight Loss in HIV Disease


FIGURE 2.

Algorithm for the evaluation and treatment of weight loss in patients with HIV disease. (CNS = central nervous system; HIV = human immunodeficiency virus; UGI = upper gastrointestinal)

MEDICAL CONSIDERATIONS

Intensive antiretroviral therapy should be instituted in patients who are not already receiving it, and antiretroviral therapy should be augmented in those who continue to have detectable viral loads. Quantitative plasma HIV RNA should be assessed, since active viral replication is associated with increased resting energy expenditure and may increase the amount of weight loss.11 The goal of therapy should be to maintain the plasma HIV RNA below detectable limits, preferably less than 50 copies per mL. Consistent with current guidelines, changes in antiretroviral therapy should involve, if possible, the introduction of at least two agents not previously used by the patient without waiting to achieve control of opportunistic disease.

Recent reports have implicated protease inhibitors in the development of glucose intolerance, hypertriglyceridemia, hypercholesterolemia and abnormal central fat accumulations that occur in association with peripheral wasting.4,5 Close monitoring for such disorders is required in patients receiving protease inhibitors. However, unless patient safety or preference dictates otherwise, there currently is no reason to discontinue protease inhibitor therapy, especially in patients otherwise benefiting from this type of agent. However, HMG-CoA reductase inhibitors should be avoided in patients with hypercholesterolemia until concerns about possible interactions with protease inhibitors are clarified. Fibrates, such as gemfibrozil (Lopid), and niacin are probably safe in patients receiving protease inhibitors. Alternatively, use of combination antiretroviral regimens that do not contain protease inhibitors may be considered.

Opportunistic diseases should be aggressively treated as soon as they are diagnosed. Measures to stimulate the patient's appetite, institution of enteral or even parenteral feeding in the case of a severe malabsorptive state and control of fever should accompany treatment of opportunistic pathology as required.

DRUG THERAPY FOR WASTING SYNDROME

Table 4 summarizes the different types of drugs used in the treatment of HIV-related wasting syndrome. The use of appetite stimulants and antiemetics in conjunction with caloric supplementation has long been considered a mainstay of therapy. In planning the treatment approach, it is important to differentiate between nausea and anorexia. In addition, underlying causes of gastrointestinal symptoms, such as drug toxicity, should be sought and resolved whenever possible.

TABLE 4

Drug Therapy for Wasting Syndrome in HIV Disease

Drug Dosage Side effects Comments

Appetite stimulants

Megestrol (Megace)

800 mg once daily

Mood changes, fat gain, edema, amenorrhea

No survival advantage demonstrated, contraindicated in pregnancy

Dronabinol (Marinol)

2.5 to 10 mg four times daily

Sedation, confusion

Potential for psychologic dependence

Cyproheptadine (Periactin)

4 mg three times daily

Sedation, anticholinergic effects

Anecdotal reports only

Anabolic agents

Oxandrolone (Oxandrin)

20 mg once daily

Cholestatic jaundice, peliosis hepatis, androgenic effects

Low androgenic effects, oral dosing

Nandrolone (Deca-Durabolin)

100 mg IM every 2 weeks

Cholestatic jaundice, peliosis hepatis, androgenic effects

Low androgenic effects, parenteral dosing only, low cost

Oxymetholone (Anadrol-50)

50 mg twice daily

Cholestatic jaundice, peliosis hepatis, androgenic effects

Little data in HIV

Testosterone

100 to 400 mg IM every 1 to 2 weeks

Cholestatic jaundice, peliosis hepatis, androgenic effects

High androgenic effects

Androderm

2.5-mg patch once daily

Local reaction to patches

High androgenic effects, expensive

Testoderm

6-mg patch once daily

rhGH (Humatrope)

0.1 mg per kg (up to 6 mg per day) SC once daily

Edema, arthralgia, hyperglycemia

Expensive, no survival advantage

Other

Thalidomide (Thalomid)

50 to 200 mg once daily

Teratogenic, sedation, neuropathy, dry mouth, hepatotoxic

Expensive, possible teratogenicity, no long-term or efficacy data


HIV = human immunodeficiency virus; IM = intramuscularly; rhGH = recombinant human growth hormone; SC = subcutaneously.

TABLE 4   Drug Therapy for Wasting Syndrome in HIV Disease

View Table

TABLE 4

Drug Therapy for Wasting Syndrome in HIV Disease

Drug Dosage Side effects Comments

Appetite stimulants

Megestrol (Megace)

800 mg once daily

Mood changes, fat gain, edema, amenorrhea

No survival advantage demonstrated, contraindicated in pregnancy

Dronabinol (Marinol)

2.5 to 10 mg four times daily

Sedation, confusion

Potential for psychologic dependence

Cyproheptadine (Periactin)

4 mg three times daily

Sedation, anticholinergic effects

Anecdotal reports only

Anabolic agents

Oxandrolone (Oxandrin)

20 mg once daily

Cholestatic jaundice, peliosis hepatis, androgenic effects

Low androgenic effects, oral dosing

Nandrolone (Deca-Durabolin)

100 mg IM every 2 weeks

Cholestatic jaundice, peliosis hepatis, androgenic effects

Low androgenic effects, parenteral dosing only, low cost

Oxymetholone (Anadrol-50)

50 mg twice daily

Cholestatic jaundice, peliosis hepatis, androgenic effects

Little data in HIV

Testosterone

100 to 400 mg IM every 1 to 2 weeks

Cholestatic jaundice, peliosis hepatis, androgenic effects

High androgenic effects

Androderm

2.5-mg patch once daily

Local reaction to patches

High androgenic effects, expensive

Testoderm

6-mg patch once daily

rhGH (Humatrope)

0.1 mg per kg (up to 6 mg per day) SC once daily

Edema, arthralgia, hyperglycemia

Expensive, no survival advantage

Other

Thalidomide (Thalomid)

50 to 200 mg once daily

Teratogenic, sedation, neuropathy, dry mouth, hepatotoxic

Expensive, possible teratogenicity, no long-term or efficacy data


HIV = human immunodeficiency virus; IM = intramuscularly; rhGH = recombinant human growth hormone; SC = subcutaneously.

Appetite Stimulants. Megestrol (Megace), a progestin used in the treatment of breast cancer, has been shown in anorectic patients to improve appetite, quality of life and total body weight.12 The weight that is gained, however, is primarily fat, possibly because of down regulation of testosterone production,13 and use of megestrol has not been found to improve survival in patients with AIDS-related cachexia.14 Use of dronabinol (Marinol), a cannabinoid naturally present in marijuana, controls nausea and improves appetite and body weight (mainly fat).15 Its effect on survival has not been evaluated.

Anabolic Agents. Androgens—particularly oxandrolone (Oxandrin), nandrolone (Deca-Durabolin), oxymetholone (Anadrol-50) and testosterone—are used to increase body cell mass in patients with wasting syndrome, although there are no accepted standards for indications, dosages and duration of therapy. Small studies of HIV-positive men have shown that body cell mass increases in response to supraphysiologic doses of testosterone,16,17 consistent with the results of studies in uninfected men.18 The clinical implications of this increase and the long-term safety of androgen administration, especially in females, are unknown. Until these issues are clarified, administration of androgens to help control HIV-related wasting should be reserved for use in men with hypogonadism and in patients who fail to respond to other therapies.

Recombinant human growth hormone (rhGH; Humatrope) is labeled by the U.S. Food and Drug Administration for the treatment of AIDS-related wasting syndrome, although its high cost (average wholesale price: $210 for each 5-mg single-dose vial) limits the availability of this therapy. A 12-week study revealed that rhGH, in a dosage of 0.1 mg per kg per day, resulted in weight gain, increased lean body mass, decreased body fat and improvement in treadmill performance in patients who had experienced at least a 10 percent weight loss.19 In another study of rhGH,20 no differences were found in health status, CD4+ cell count, plasma HIV RNA or use of medical resources among treated and untreated patients, and lower dosages did not appear to be efficacious.

The safety and efficacy of long-term rhGH therapy and its impact on survival are unclear. Also unknown is the question of whether similar outcomes can be achieved with other, less expensive interventions. It seems advisable, therefore, to reserve the use of rhGH for patients who are undergoing unexplained significant weight loss, who have not responded to other therapies and who require short-term treatment to maintain body cell mass during acute infection.

Thalidomide. Thalidomide (Thalomid), an inhibitor of TNF-α, is effective in the treatment of HIV-related aphthous ulcers21 and was shown in short-term studies to be associated with significant weight gain.21 Use of thalidomide in the treatment of wasting syndrome in the absence of aphthous stomatitis is therefore being investigated. However, because toxicity from this drug can be significant, its utility may be limited to only those situations in which other therapies have failed. Male and female patients must be counseled about its teratogenic potential.

DENTAL CARE

Treatment of painful or obstructive dental disease may significantly improve nutritional intake. Periodontitis and gingivitis may be prevented with regular use of a topical antiseptic and should be aggressively treated when present. All patients with HIV disease should be referred for regular preventive dental care.

NUTRITION

The best strategy to prevent wasting is to incorporate the patient's food preferences into the goal of an adequate intake of calories and protein to meet metabolic needs (Table 5). To preserve small bowel function, solid food is recommended whenever possible.22 Food texture and temperature should be optimized to reduce pain or dysfunctional deglutition. For example, if oral inflammation is present, it may be helpful to avoid hard foods. Micronutrients in the form of multivitamin preparations should be routinely prescribed. Patients should be counseled about safe food procurement, storage and preparation to reduce the risk of exposure to intestinal pathogens.23 Specific recommendations include using purified water for washing, brushing and rinsing fresh produce and other foods if the water supply is untreated and avoiding raw, undercooked and unpasteurized foods.

TABLE 5

General Recommendations for Nutritional Therapy in Patients with HIV-Related Wasting Syndrome

General dietary recommendations

For females: intake of 2,500 to 3,000 kcal per day, with 1.2 g per kg of protein per day

For males: intake of 3,000 to 3,500 kcal per day, with 1.2 g per kg of protein per day

Daily micronutrient supplement should include vitamins A, B6, B12 and selenium.

Nutritional recommendations for problems related to wasting syndrome

Oral inflammation

Avoid temperature extremes, highly seasoned foods and hard foods (e.g., chips); drink beverages through a straw.

Anorexia

Consume mild flavors, foods at a moderate temperature and appetizing foods. Oral nutritional supplements* such as Carnation Instant Breakfast, Ensure, Sustacal and Lipisorb (for oral and tube feeding) may be helpful if dietary intake is insufficient for sustaining weight.

Nausea

Consume mild flavors, foods at a moderate temperature and appetizing foods. Useful oral supplements* include Nubasics (bar and soup), Lipisorb, Resource and Scandishake. Lipisorb and Peptamen may be useful in patients requiring tube feeding.

Diarrhea

Consume lactose-free, low-fiber, low-osmolality diet. Useful oral supplements* include Isosource HN, Lipisorb (for oral or tube feeding) and Sustacal.

Steatorrhea

Consume low-fat diet; supplements should contain medium-chain triglycerides. Useful supplements* include Lipisorb for oral or tube feeding and Peptamen and Reabilan for tube feeding.


HIV = human immunodeficiency virus.

*—Nutritional supplements should be used only in patients whose dietary intake is inadequate for sustaining weight.

TABLE 5   General Recommendations for Nutritional Therapy in Patients with HIV-Related Wasting Syndrome

View Table

TABLE 5

General Recommendations for Nutritional Therapy in Patients with HIV-Related Wasting Syndrome

General dietary recommendations

For females: intake of 2,500 to 3,000 kcal per day, with 1.2 g per kg of protein per day

For males: intake of 3,000 to 3,500 kcal per day, with 1.2 g per kg of protein per day

Daily micronutrient supplement should include vitamins A, B6, B12 and selenium.

Nutritional recommendations for problems related to wasting syndrome

Oral inflammation

Avoid temperature extremes, highly seasoned foods and hard foods (e.g., chips); drink beverages through a straw.

Anorexia

Consume mild flavors, foods at a moderate temperature and appetizing foods. Oral nutritional supplements* such as Carnation Instant Breakfast, Ensure, Sustacal and Lipisorb (for oral and tube feeding) may be helpful if dietary intake is insufficient for sustaining weight.

Nausea

Consume mild flavors, foods at a moderate temperature and appetizing foods. Useful oral supplements* include Nubasics (bar and soup), Lipisorb, Resource and Scandishake. Lipisorb and Peptamen may be useful in patients requiring tube feeding.

Diarrhea

Consume lactose-free, low-fiber, low-osmolality diet. Useful oral supplements* include Isosource HN, Lipisorb (for oral or tube feeding) and Sustacal.

Steatorrhea

Consume low-fat diet; supplements should contain medium-chain triglycerides. Useful supplements* include Lipisorb for oral or tube feeding and Peptamen and Reabilan for tube feeding.


HIV = human immunodeficiency virus.

*—Nutritional supplements should be used only in patients whose dietary intake is inadequate for sustaining weight.

Caloric and protein supplements may be useful if they do not supplant more nutritionally diverse foods and are provided in a palatable form that can be easily ingested. Nutritional supplements are not useful in the prevention of weight loss and should be reserved for use in patients in whom normal dietary intake is clearly inadequate for sustaining weight.

In patients whose oral intake remains below 25 percent of the calculated caloric goal for more than three days, nocturnal nasogastric or percutaneous endoscopic gastronomy tube feedings may be required.24 Because of the increased risk of infection25 and the high cost of total parenteral nutrition, the latter should be reserved for use in patients with significant malabsorption or for whom adequate enteral intake is not possible.

EXERCISE

Exercise that provides a workout of skeletal muscle should be encouraged in patients able to tolerate it (Table 3 and accompanying patient information handout). Data demonstrating synergy between resistance exercise and anabolic steroids in enhancing body cell mass and strength suggest that exercise may be an important adjunctive therapy.17,18 Referral to an exercise physiologist or physical therapist should be considered.

Final Comment

Treatment of HIV-related wasting syndrome requires vigilance in looking for the early signs of its onset. Regular evaluation of patients with HIV infection must include a review of nutritional intake and physical activity, a review of symptoms to elicit any symptoms of occult opportunistic disease and virologic monitoring. Aggressive antiretroviral therapy should be used to minimize the HIV load. Another important part of follow-up includes ongoing patient education to enhance adherence to medication regimens, nutritional intake and exercise.

In addition, collaboration among the primary care clinician, dietitian, subspecialists, exercise physiologist or physical therapist, dentist, pharmacist, household caregivers and patient is important to ensure that a multifaceted approach to the condition is adequately coordinated. Pharmacologic intervention should, in general, be reserved for use in patients failing other therapies.

With early identification and aggressive treatment, wasting syndrome in HIV disease is a manageable condition and need not inevitably result in disability or death. Aggressive treatment often results in complete restoration of the patient's baseline weight and health.

The Authors

BRUCE WILLIAMS, M.D., M.P.H., is a family physician and associate professor in the Department of Medicine and the Department of Family and Community Medicine at the University of New Mexico School of Medicine, Albuquerque. He is a primary care clinician in the University of New Mexico HIV Clinic, medical director of Partners in Care, a statewide Ryan White Title III program, and principal investigator of Partners in Research/New Mexico, a unit of the Terry Beirn Community Programs for Clinical Research on AIDS.

DEBRA WATERS, PH.D., is a research scientist and exercise physiologist in the Department of Medicine at the University of New Mexico School of Medicine. Her research interests include the effects of recombinant human growth hormone on HIV wasting syndrome, use of magnetic resonance imaging spectroscopy in elucidating mitochondrial and metabolic dysfunction in HIV wasting syndrome, and age-related sarcopenia.

KATHERINE PARKER, M.S., R.D., is the manager of nutritional research at the General Clinical Research Center at the University of New Mexico. Her research interests include body composition, anthropometrics and nutritional habits of patients with chronic disease, including HIV infection and hantavirus pulmonary syndrome.

Address correspondence to Bruce Williams, M.D., M.P.H., Department of Medicine, University of New Mexico School of Medicine, 2211 Lomas N.E., Albuquerque, NM 87131. Reprints are not available from the authors.

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