- Email: [email protected]
HIV-Associated Wasting
HIV-Associated Wasting Joyce K. Keithley, DNSc, RN, FAAN Barbara Swanson, PhD, RN, FAAN HIV-associated wasting continues to be a problem, particularly in individuals who use drugs and have food insecurity, high viral loads, and low-income levels. There is some evidence to suggest that nutrition counseling with or without oral nutritional supplements, anabolic/androgenic agents, and aerobic exercise with or without resistive exercise are likely to be effective in combating HIV-associated wasting. Limited or no evidence exists for the efficacy of herbal supplements, appetite stimulants, macronutrient and micronutrient supplements, and cytokine modulators for wasting in HIV-infected individuals. Most studies reviewed were of uneven quality, and few looked at significant endpoints such as disease progression and mortality. (Journal of the Association of Nurses in AIDS Care, 24, S103-S111) Copyright Ó 2013 Association of Nurses in AIDS Care Key words: anabolic/androgenic agents, exercise, nutrition, supplements, wasting
In 1987, the Centers for Disease Control and Prevention (Centers for Disease Control and Prevention, 1987) defined HIV wasting syndrome as the involuntary loss of greater than 10% of body weight accompanied by chronic diarrhea, weakness, or fever for 30 days or more in the absence of concurrent illness. Since effective antiretroviral therapy (ART) has become available, several other definitions have been proposed (Mangili, Murman, Zampini, & Wanke, 2006; Polsky, Kotler, & Steinhart, 2001), which generally incorporate one or more of the following criteria: (a) unintentional weight loss of more than 5%–10%, (b) body mass index (BMI) less than 20, and (c) body cell mass loss of more than 5%. In clinical practice, HIV-associated
wasting is usually defined as any unintentional weight loss, characterized by loss of muscle mass in men and a loss of both muscle and fat mass in women, which is predictive of disease progression and mortality (Kotler, Wang, & Pierson, 1985; Siddiqui et al., 2009; Tang, Jacobson, Spiegelman, Knox, & Wanke, 2005).
Prevalence The prevalence of HIV-associated wasting was estimated at 30% during the pre-ART era of the HIV epidemic (Nahlen et al., 1993; Smit et al., 2002). While the prevalence has declined, wasting still occurs, especially in injection drug users (IDUs) and individuals with food insecurity, high viral loads, and low-income levels (,$500/month; Campa et al., 2005; Mangili et al., 2006; Siddiqui et al., 2009). A number of factors influence wasting prevalence, including reduced food intake, malabsorption, endocrine abnormalities, metabolic disorders, and virologic and immune factors (Campa et al., 2005; Dudgeon et al., 2006; Grunfeld et al., 1992).
Assessment and Clinical Measurement Tools Optimal nutrition status supports optimal immune function (Campa et al., 2005). There are many approaches to nutrition status assessment, including the ABCD approach that incorporates Joyce K. Keithley, DNSc, RN, FAAN, is a Professor at Rush University College of Nursing, Chicago, Illinois. Barbara Swanson, PhD, RN, FAAN, is a Professor at Rush University College of Nursing, Chicago, Illinois, USA.
JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE, Vol. 24, No. 1S, January/February 2013, S103-S111 http://dx.doi.org/10.1016/j.jana.2012.06.013 Copyright Ó 2013 Association of Nurses in AIDS Care
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anthropometric, biochemical, clinical, and dietary measures. A summary of key parameters within each of these measures can be found in Table 1. A nutrition status assessment should be performed two to three times per year to identify individuals who are at risk for, or have, wasting (Polsky et al., 2001). Anthropometric measures include the evaluation of height, weight, and body composition. An unintentional weight loss of greater than 5%–10% over any time frame is considered clinically significant (Mangili et al., 2006; Polsky et al., 2001). BMI, a marker of optimal weight for height, is calculated from weight in kilograms/height in meters squared. Automatic BMI calculators are available online for easy calculation. A BMI lower than 20 in association with loss of lean body mass (LBM) is indicative of wasting (Mangili et al., 2006; Polsky et al., 2001). Body composition measures assess body fat and muscle distribution and can be measured using bioelectrical impedance analysis and triceps skinfold and waist and hip circumferences (Table 1). Measures lower than 90%–95% of normal are indicative of wasting (Kotler et al., 1985; Polsky et al., 2001). Biochemical assessment includes nutrition-related laboratory parameters such as hemoglobin and blood glucose (Table 1). Deficiencies may contribute to the wasting process and may adversely affect immune function (Campa et al., 2005). The clinical history and physical examination collect information about health problems that may contribute to wasting, such as drug-nutrient interactions (Table 2) and physical signs of wasting, such as loss of subcutaneous fat and muscle wasting. Several methods for collecting the dietary history are available, including 24-hour recall, food frequency questionnaire, food diaries, and direct observation. The 24-hour recall is the quickest and most widely used technique, although all techniques provide useful information. As part of the dietary history, it is also important to assess food intolerances and nutrition-related factors and symptoms, such as anorexia and depression. A variety of tools are available for determining nutrition status. One tool adapted and tested specifically for use in persons living with HIV infection (PLWH) is the Subjective Global Assessment for HIV-Infected Individuals (SGA-HIV; Bowers & Dols, 1996). An overall SGA-HIV rating can be made based on data easily obtained from the medical
Table 1.
Anthropometric, General Health, and Dietary Assessment Measures
Anthropometric measures Height, weight, body mass index (BMI) Bioelectrical impedance analysis (BIA): body cell mass (BCM), fat mass, body water Triceps skinfold, waist and hip circumference Biochemical measures (nutrition-related) Hemoglobin/hematocrit Total protein, albumin, liver, and renal function Fasting blood glucose and lipids Clinical history and examination Medications that impact nutrition Gastrointestinal co-morbidities Endocrine co-morbidities Secondary infections, such as thrush Dietary history Usual dietary intake and patterns Estimated energy intake Food allergies/intolerances/restrictions, use of dietary supplements Factors & symptoms that affect intake (e.g., poor appetite, fatigue, substance abuse, food insecurity, depression, inadequate nutrition knowledge)
history and physical examination (Figure 1). Individuals who are mildly-to-moderately malnourished or severely malnourished require additional followup by nurses, dietitians, and other members of the health care team to address nutrition-related issues.
What Interventions are Effective for Preventing and Treating Wasting in PLWH? Recommended for Practice Indications for nutrition intervention. Nutrition intervention is indicated for: (a) significant weight loss (.5% in 3 months), (b) significant body cell mass loss (.5% in 3 months), and (c) BMI lower than 18.5 kg/m2. Recommended protein intake is 1.25–1.5 g/kg of body weight; recommended energy intake (calories from protein, carbohydrate, and fat) is 25 kcal/kg of body weight (Ockenga et al., 2006). Clinical guidelines established by the European Society for Parenteral and Enteral Nutrition (Ockenga et al., 2006) identified indications for nutrient intervention, as well as recommendations for protein and overall energy intake. When significant weight loss, significant body cell mass depletion,
Keithley, Swanson / Wasting Table 2.
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Antiretroviral Medication Administration: Recommended Food Intake Drug
Multi-class combination agents Efavirenz/emtricitabine/tenofovir (AtriplaÒ) Emtricitabine/rilpivirine/tenofovir (CompleraÒ) Nucleoside reverse transcriptase inhibitors Lamivudine/zidovudine (CombivirÒ) Emtricitabine (EmtrivaÒ) Lamivudine (EpivirÒ) Abacavir/lamivudine (EpzicomÒ) Zidovudine (RetrovirÒ) Abacavir/lamivudine/zidovudine (TrizivirÒ) Tenofovir/emtricitabine (TruvadaÒ) Didanosine (VidexÒ) Tenofovir (VireadÒ) Stavudine (ZeritÒ) Abacavir (ZiagenÒ) Nonnucleoside reverse transcriptase inhibitors Rilpivirine (EdurantÒ) Etravirine (IntelenceÒ) Delavirdine (RescriptorÒ) Efavirenz (SustivaÒ) Nevirapine (ViramuneÒ) Protease inhibitors Amprenavir (AgeneraseÒ) Tipranavir (AptivusÒ) Indinavir (CrixivanÒ) Saquinavir (InviraseÒ) Lopinavir/ritonavir (KaletraÒ) Fosamprenavir (LexivaÒ) Darunavir (PrezistaÒ) Atazanavir (ReyatazÒ) Nelfinavir (ViraceptÒ) Entry inhibitor Maraviroc (SelzentryÒ) Integrase inhibitor Raltegravir (IsentressÒ)
Administration Recommendation Take with food Take on an empty stomach May be taken with or without food May be taken with or without food May be taken with or without food May be taken with or without food May be taken with or without food May be taken with or without food May be taken with or without food Take on an empty stomach May be taken with or without food May be taken with or without food May be taken with or without food Take with food Take after eating a meal May be taken with or without food Take on an empty stomach May be taken with or without food May be taken with or without food; do not take with a high fat meal May be taken with or without food Take without food or with a light meal; drink at least 48 oz of fluids/day to prevent kidney stones Take within 2 hours of a full meal May be taken with or without food May be taken with or without food Take with food Take with food Take with food May be taken with or without food May be taken with or without food
and low BMI occur, nutrition intervention that focuses on maximizing food intake is recommended. Meals should incorporate individual preferences and high calorie/high protein foods such as cheese and peanut butter. The European Society for Parenteral and Enteral Nutrition guidelines were based on a review of relevant publications since 1985, as well as interdisciplinary group expert opinion. Likely to be Effective Nutrition counseling. In disease-related wasting, nutrition counseling with or without oral nutritional
supplements may improve body weight, composition, and grip strength, an early indicator of nutritional status. Areas of nutrition counseling include the importance of maintaining body weight and eating nutritious foods (i.e., foods rich in protein, calories, vitamins, minerals), preventing drug-nutrient interactions (Table 2), and managing nutrition-related symptoms and barriers, such as lack of appetite and living in a food desert (Polsky et al., 2001). In a meta-analysis of 45 clinical trials, Baldwin and Weekes (2011) suggested that nutrition counseling with or without oral nutrition supplements significantly improved weight gain (11.47–3.75
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Patient Name:________________________
Patient ID:______________
Date:___________
Part 1: Medical History 1. Weight Change A. Overall change in past 6 months: __________kgs B. Percent change: __________Gain - <5% loss __________5%-10% loss __________>10% loss C. Change in past 2 weeks: __________Increase __________No change __________Decrease D. Height________; Weight_______ Weight 6 mo ago: __________ Weight 12 mo ago: __________ 2. Dietary Intake A. Overall change: __________No change; _________Change _________ B. Type of change: __________ More: _________ Less: __________Much less __________ Suboptimal solid diet _________ Hypocaloric liquids __________ Full liquid diet __________Starvation C. Duration: __________Weeks 3. Gastrointestinal Symptoms (persisting for >2 weeks) _________None; _________Nausea; ________Vomiting; ________Diarrhea; _________Anorexia; ________Constipation; _________Oral sores; _________Dysphagia; _________Taste changes 4. Functional Impairment (nutritionally related) A. Overall impairment: _________None (no limitations) ________ Mild (not normal self; able to do fairly normal activities) ________ Moderate (not up to most things; > ½ day in bed/chair) _________Severe (primarily bedridden) B. Change in past 2 weeks: _________ Improved _________ No Change _________ Regressed Part 2: Physical Examination 5. Evidence of: Loss of subcutaneous fat Muscle wasting Edema Ascites (renal/ hepatic)
____Normal;____ Mild; ____Moderate; ____Severe ____Normal; ____Mild; ____ Moderate; ____Severe ____Normal; ____Mild; ____ Moderate; ____Severe ____Normal; ____Mild; ____Moderate; ____Severe
Part 3: SGA Rating (check one) A. A. Well-nourished B. Mild to moderately malnourished C. Severely malnourished Figure 1. Revised subjective global assessment for HIV-infected individuals. From: Bowers, J. M., & Dols, C. L. (1996). Subjective Global Assessment in HIV-infected patients. Journal of the Association of Nurses in AIDS Care, 7(4). 83–89. http://dx.doi. org/10.1016/S1055-3290(96)80062-8. Republished with permission from Elsevier Inc.
kg), triceps skinfold thickness (1.40–1.22 mm), midarm muscle circumference (.81–.89 mm), and hand grip strength (11.67 kg). Qualified nutrition counseling can be provided by registered dietitians, die-
tetic technicians, and other health care professionals with specialized training in nutrition. Oral supplements are available in the form of drinks, candy bars, and soups that are tasty and easy to use,
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including specialized products for patients with specific intolerances (e.g., lactose intolerance, fat malabsorption). Studies in the meta-analysis were of low-to-moderate quality, with varied interventions and patient groups (Baldwin & Weekes, 2011). No evidence of survival benefits related to nutrition counseling with or without oral nutritional supplements was found, and a lack of evidence related to effects on quality of life and functional status was reported. Anabolic/androgenic agents. Anabolic steroids have been associated with gains in weight and lean body mass, as well as improvements in parameters of physical performance. No adverse effects on viral replication have been reported. In men, treatment with testosterone is associated with increased fat and lean body mass, but increased fat mass only in women (Looby, Collins, Lee, & Grinspoon, 2009; Moyle et al., 2004). Anabolic/androgenic agents have been used to promote weight gain, especially LBM. A metaanalysis of 18 studies concluded that recombinant human growth hormone, anabolic steroids, and testosterone were equally efficacious in increasing LBM in HIV-related wasting (DEXA-measured mean LBM gain 5 2.74–3.3 kg; Looby et al., 2009). Treatment with recombinant human growth hormone may confer the additional benefit of improving functional performance and quality of life (Moyle et al., 2004). There is some evidence for gender-specific effects. In men, short-term treatment with testosterone (12 weeks) was associated with increased fat and LBM, but testosterone increased fat mass (12 kg) only in women. In women with low testosterone levels, however, long-term testosterone treatment (18 months) increased lean mass (11.8 kg) and had no effect on fat mass (Looby et al., 2009). Although anabolic/androgenic agents are likely effective for the management of HIV-associated wasting, the gains in LBM were found to be small and of questionable clinical relevance. Moreover, methodological limitations of the extant literature have precluded advancing treatment recommendations. These limitations included short treatment durations, different formulations of study drug, inadequate statistical power to test a range of doses, non-
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standardized operational definitions of wasting, and nonequivalent measures of body composition (Looby et al., 2009; Moyle et al., 2004). Exercise. Early concerns about the safety of aerobic exercise on virological and immune outcomes have been discredited. A meta-analysis of 14 studies concluded that aerobic and resistive exercise, both alone and in combination, were associated with increased muscle mass (1.1 to 6.9 kg) and improvements in cardiovascular fitness and depression; improvements were contingent upon adhering to an activity regimen for a minimum of 20 minutes/day, 3 days/week for 5 weeks. No deleterious immunological or virological effects were found (O’Brien, Nixon, Tynan, & Glazier, 2010). Resistive exercise alone for 16 weeks has been shown to increase LBM and muscle strength and to reduce serum triglycerides (Yaresheski et al., 2001). Persistent adherence to aerobic and/or resistive exercise is a safe and effective approach for favorably modulating body composition and metabolic parameters in HIV-associated wasting. Effectiveness Not Established Macronutrient supplementation. In a metaanalysis of eight randomized controlled trials (Mahlungulu, Grobler, Visser, & Volmink, 2007), macronutrient supplementation significantly improved overall calorie (1367 kcal/day) and protein intake (117 g/day) compared with individuals who did not receive supplementation. However, no effect on weight, fat mass, or fat-free mass was noted. Studies in this review were limited by small sample sizes, relatively high attrition rates, and differences in macronutrient supplements and HIV disease stage. Effects of balanced nutritional supplements on disease progression and survival are equivocal at this time. Herbal supplements. No published meta-analysis or integrative reviews were found specific to the safety and efficacy of herbal supplements to combat wasting in HIV disease. A recent study found that herbal supplement use was infrequent in PLWH, and that the most commonly used dietary supplements were vitamins, calcium, and omega-3 fatty acids (Aghdassi, Bondhar, Salit, Tinmouth, & Allard, 2009).
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Appetite stimulants. Megestrol acetate (MA, Megace ESÒ; Strativa Pharmaceuticals, Woodcliff Lake, NJ) is U.S. Food and Drug Administration (FDA)-approved to manage HIV-associated weight loss. Evidence has suggested that most of the weight gain is in the form of fat mass, possibly due to the hypogonadic effect of MA that favors gain of fat mass over lean mass (Oster et al., 1994; Von Roenn et al., 1994), and co-administration of testosterone does not increase LBM (Mulligan et al., 2007). The recommended dosage is 625 mg/day and the durability of weight gain once MA is discontinued is unknown. Interactions with certain antiretroviral medications have been reported. Co-administration of etravirine has been associated with slight increases in plasma estradiol, while decreased plasma concentrations of estradiol and progestin have been observed with co-administration of efavirenz and nevirapine, both of which are known inducers of CYP3A4. The latter may potentially affect the efficacy of oral contraceptives. A recent systematic review concluded that the lack of rigorous studies in PLWH precludes recommendations for the use of MA to manage HIV-related wasting (Berenstein & Ortiz, 2005). Dronabinol is FDA-approved to manage HIVassociated anorexia. The recommended dosage is 2.5 mg twice a day. Limited data have shown mixed findings related to appetite improvement and no evidence for weight gain (Beal et al., 1995; Oster et al., 1994; Struwe et al., 1993). Long-term use (12 months) has been associated with stable body weight in late-stage AIDS patients, but 44% of study participants showed expected, non-life-threatening, adverse central nervous system effects (Beal et al., 1997). Effectiveness Unlikely Micronutrient supplementation. Vitamin A, vitamin D, and zinc supplements have not been associated with reversal of wasting in HIV disease. A meta-analysis of six vitamin A clinical trials, one vitamin D clinical trial, two zinc clinical trials, three selenium clinical trials, and 10 multiple supplement trials in adults revealed no effect of any of these vitamins or minerals on wasting (Irlam, Visser, Rollins, & Siegfried, 2010). Limited evidence suggested that selenium supplements could be associated with
reductions in viral load, and equivocal evidence suggested that multiple supplements were associated with enhanced cellular immunity. Studies included in the meta-analysis varied in methodological quality, especially in terms of incomplete outcome reporting, selective reporting, and other biases. Cytokine modulators. Because HIV-associated wasting has been linked to overproduction of inflammatory cytokines (Rivera et al., 2001; Roubenoff et al., 2002), cytokine suppressors have been investigated for their ability to restore LBM. In a randomized, placebo-controlled trial, an 8-week course of thalidomide at a dose of 100 or 200 mg/day was associated with modest weight gains of 2.2 and 1.5 kg, respectively, but it also increased plasma concentrations of HIV RNA (Kaplan et al., 2000). In a clinical trial of thalidomide to manage aphthous ulcers, participants in the treatment group showed increases in plasma concentrations of HIV RNA and tumor necrosis factor-a. Trials of other cytokine modulators, including omega-3 fatty acids (Hellerstein et al., 1996) and pentoxifylline (Wallis et al., 1996), have shown no effects for weight or LBM gain.
Case Study Case Description DT is a 26-year-old white man who presents to a municipal infectious disease clinic with a 3-month history of weight loss. Diagnosed with HIV infection 6 years ago, DT lives in a homeless shelter, has a history of IDU, and drinks 2–3 beers/day. Baseline nutrition assessment reveals: height, 5 feet 8 inches; medium frame size; current weight 120 pounds, compared to a usual weight of 140 pounds; and a BMI of 18. Bioelectrical impedance analysis indicates mild dehydration and body cell mass depletion. His dietary intake for the past month was approximately 1,000 kcal/day and consisted primarily of carbonated beverages and fast foods. His estimated resting energy expenditure is 2,200 kcal/day. DT states that he does not have a reliable food source and does not always remember to take his ART medications. Laboratory findings include: viral load . 100,000 copies/mL, CD4 1 T-cell count equals 225 cells/mm3,
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and hemoglobin equals 12.1 g/dL. DT denies a recent history of diarrhea or secondary infections. Recommended for Practice DT meets all of the indications for nutrition intervention, including significant weight loss over the previous 3 months (20 pounds or 14% loss), body cell mass depletion, and a BMI , 18.5 kg/m2. Nutrition interventions that provide 1.25–1.5 grams protein/kg of body weight and 25 kcal/kg of body weight are recommended. Likely to be Effective Initial visit. Complete nutrition assessment using SGA-HIV and ABCD assessment guides to identify wasting etiologies and nutrition-related problems and barriers are warranted. It will help to collaborate with the dietitian, case manager, and social worker to conduct the initial assessment and develop strategies to improve nutrition intake and weight gain, taking into consideration DT’s lifestyle and resources. It is important to provide nutrition counseling and specific options for a steady food source of high-protein and high-calorie meals, including oral nutritional supplements. Options might include specific meal arrangements with the homeless shelter and programs that provide free oral nutritional supplements. 1-month follow-up. The nurse should assess for any changes in nutritional status, focusing on body weight, laboratory parameters, and any new nutrition problems or barriers. If no improvement is noted, screen for undiagnosed wasting etiologies, such as oral lesions, nausea, and pain. Evaluate effectiveness of meal options and use of supplements. Consider aerobic exercise with or without resistive exercise to improve body cell mass. 3-month follow-up. Use assessments and interventions as noted above and adjust plan based on changes in nutritional status. A weight gain of 1–2 pounds/month or 3–6 pounds/3 months is a realistic goal. Collaborate with DT and his health care team members, case manager, and others to develop strategies to address IDU, adherence, homelessness, and other issues.
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DT’s homelessness and IDU present significant challenges to combating wasting. Based on current evidence and guidelines, DT meets indications for nutrition intervention. Nutrition counseling, oral nutrition supplements, anabolic/androgenic agents, and exercise are likely to be effective in wasting reversal. Because effectiveness is either not established or unlikely, herbal supplements, macronutrient and micronutrient supplements, cytokine modulators, and appetite stimulants are not recommended. As an initial plan, reliable meal sources and oral nutrition supplements are provided. At his 1-month followup visit, DT reported adherence to the meal options and had gained 2 pounds using the meal and oral nutrition supplement options provided. At his 3-month visit, weight gain continued at a rate of 1– 2 pounds/month. The health care team recommended that DT continue on the same nutrition plan and consider exercise to promote lean body mass gain.
Clinical Considerations Wasting remains a common problem in HIVinfected individuals, especially among injection drug users and those who live below the poverty line, have food insecurity, and have high viral loads. Assessment of nutrition status using valid and reliable tools at regular intervals is the first step in combating HIV-associated wasting. Current evidence and guidelines support the use of nutrition counseling, oral nutrition supplements, anabolic/androgenic agents, and exercise as likely to be effective in wasting reversal. Effectiveness has not been established or is unlikely for herbal supplements, macronutrient and micronutrient supplements, cytokine modulators, and appetite stimulants at this time.
Disclosures The authors report no real or perceived vested interests that relate to this article (including relationships
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with pharmaceutical companies, biomedical device manufacturers, grantors, or other entities whose products or services are related to topics covered in this manuscript) that could be construed as a conflict of interest.
References Aghdassi, E., Bondhar, H., Salit, I. E., Tinmouth, J., & Allard, J. P. (2009). A survey on the usage of supplements in Canadian patients living with HIV. Current HIV Research, 9, 555-561. http://dx.doi.org/10.2174/157016209789346200 Baldwin, C., & Weekes, C. E. (2011). Dietary advice with or without oral nutritional supplements for disease-related malnutrition in adults. Cochrane Database of Systematic Reviews, 9 http://dx.doi.org/10.1002/14651858.CD002008. pub4 Art. No.: CD002008. Beal, J. E., Olson, R., Laubenstein, L., Morales, J. O., Bellman, P., Yangco, B., . Shepard, K. V. (1995). Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. Journal of Pain and Symptom Management, 10(2), 89-97. http://dx.doi.org/10.1016/0885-3924(94) 00117-4 Beal, J. E., Olson, R., Lefkowitz, L., Laubenstein, L., Bellman, P., Yangco, B., . Shepard, K. V. (1997). Longterm efficacy and safety of dronabinol for acquired immune deficiency syndrome-associated anorexia. Journal of Pain and Symptom Management, 14(1), 7-14. Berenstein, G., & Ortiz, Z. (2005). Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database of Systematic Reviews, 2 http://dx.doi.org/10.1002/14651858. CD004310.pub2 Art. No.: CD004310. Bowers, J. M., & Dols, C. L. (1996). Subjective global assessment in HIV-infected patients. Journal of the Association of Nurses in AIDS Care, 7(4), 83-89. http://dx.doi.org/10.1016/ S1055-3290(96)80062-8 Campa, A., Yang, Z., Lai, S., Xue, L., Phillips, J. C., Sales, S., . Baum, M. K. (2005). HIV-related wasting in HIV-infected drug users in the era of highly active antiretroviral therapy. Clinical Infectious Diseases, 41, 1179-1185. http://dx.doi.org/ 10.1086/444499 Centers for Disease Control and Prevention. (1987). Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Retrieved from http://www.cdc.gov/ mmwr/pdf/other/mmsu3601.pdf Dudgeon, W. D., Phillips, K. D., Carson, J. A., Brewer, R. B., Durstine, J. L., & Hand, G. A. (2006). Counteracting muscle wasting in HIV-infected individuals. HIV Medicine, 7(5), 299-310. Grunfeld, C., Pang, M., Shimizu, L., Shigenaga, J. K., Jensen, P., & Feingold, K. R. (1992). Resting energy expenditure, caloric intake, and short-term weight change in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. American Journal of Clinical Nutrition, 55, 455-460.
Hellerstein, M. K., Wu, K., McGrath, M., Faix, D., George, D., Shackleton, C. H., . Neese, R. A. (1996). Effects of dietary n-3 fatty acid supplementation in men with weight loss associated with the acquired immune deficiency syndrome: Relation to indices of cytokine production. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, 11(3), 257-270. Irlam, J. H., Visser, M. M. E., Rollins, N. N., & Siegfried, N. (2010). Micronutrient supplementation in children and adults with HIV infection. Cochrane Database of Systematic Reviews, 12, 1-23. http://dx.doi.org/10.1002/14651858. CD003650.pub3 Art. No.: CD003650. Kaplan, G., Thomas, S., Fierer, D. S., Mulligan, K., Haslett, P. A., Fessel, W. J., . Schambelan, M. (2000). Thalidomide for the treatment of AIDS-associated wasting. AIDS Research and Human Retroviruses, 16(14), 1345-1355. http://dx.doi.org/ 10.1089/08892220050140892 Kotler, D. P., Wang, J., & Pierson, R. N. (1985). Body composition studies in patients with the acquired immunodeficiency syndrome. American Journal of Clinical Nutrition, 42, 1255-1265. Looby, S. E. D., Collins, M., Lee, H., & Grinspoon, S. (2009). Effects of long-term testosterone administration in HIVinfected women: A randomized, placebo controlled trial. AIDS, 23(8), 951-959. http://dx.doi.org/10.1097/QAD. 0b013e3283299145 Mahlungulu, S. S. N., Grobler, L., Visser, M. M. E., & Volmink, J. (2007). Nutritional interventions for reducing morbidity and mortality in people with HIV. Cochrane Database of Systematic Reviews, 3, 1-39. http://dx.doi.org/10.1002/ 14651858.CD004536.pub2 Art. No.: CD004536. Mangili, A., Murman, D. H., Zampini, A. M., & Wanke, C. E. (2006). Nutrition and HIV infection: Review of weight loss and wasting in the era of highly active antiretroviral therapy from the Nutrition for Healthy Living Cohort. Clinical Infectious Diseases, 42, 836-842. http://dx.doi.org/10.1086/ 500398 Moyle, G. J., Shoelles, K., Fahrbach, K., Frame, D., James, K., Scheye, R., & Cure-Bolt, N. (2004). Efficacy of selected treatments of HIV wasting: A systematic review and metaanalysis. Journal of the Acquired Immune Deficiency Syndrome, 37, S262-S276. Mulligan, K., Zackin, R., Von Roenn, J. H., Chesney, M. A., Egorin, M. L., Sattler, F. R., . Schambelan, M. (2007). Testosterone supplementation of megestrol therapy does not enhance lean tissue accrual in men with human immunodeficiency virus-associated weight loss: A randomized, doubleblind, placebo-controlled multicenter trial. Journal of Clinical Endocrinology and Metabolism, 92(2), 563-570. http://dx.doi.org/10.1210/jc.2006-095 Nahlen, B. L., Chu, S. Y., Nwanyanwu, O. C., Berkelman, R. L., Martinez, S. A., & Rullan, J. V. (1993). HIV wasting syndrome in the United States. AIDS, 2, 183-186. O’Brien, K., Nixon, S., Tynan, A. M., & Glazier, G. (2010). Aerobic exercise interventions for adults living with HIV/AIDS. Cochrane Database of Systematic Reviews, 8.
Keithley, Swanson / Wasting http://dx.doi.org/10.1002/14651858.CD001796.pub3 Art. No.: CD001796. Ockenga, J., Grimble, R., Jonkers-Schuitema, C., Macallan, D., Melchior, J.-C., Sauerwein, H. P., . Suttmann, U. (2006). ESPEN guidelines on enteral nutrition: Wasting in HIV and other chronic infectious diseases. Clinical Nutrition, 25, 319-329. http://dx.doi.org/10.1016/j.clnu.2006.01.016 Oster, M. H., Enders, S. R., Samuels, S. J., Cone, L. A., Hooton, T. M., Browder, H. P., & Flynn, N. M. (1994). Megestrol acetate in patients with AIDS and cachexia. Annals of Internal Medicine, 121(6), 400-408. Polsky, B., Kotler, D., & Steinhart, C. (2001). HIV-associated wasting in the HAART era: Guidelines for assessment, diagnosis, and treatment. AIDS Patient Care and STDs, 15(8), 411-423. http://dx.doi.org/10.1089/108729101316914412 Rivera, S., Sattler, F. R., Boyd, H., Auffenberg, T., Nakao, S., & Moldawer, L. L. (2001). Urinary cytokines for assessing inflammation in HIV-associated wasting. Cytokine, 13, 305-313. http://dx.doi.org/10.1006/cyto.2000.0830 Roubenoff, R., Grinspoon, S., Skolnik, P. R., Tchetgen, E., Abad, L., Knox, T., & Gorbach, S. (2002). Role of cytokines and testosterone in regulating lean body mass and resting energy expenditure in HIV-infected men. American Journal of Physiology, Endocrinology, and Metabolism, 283, E138-E145. http://dx.doi.org/10.1152/ajpendo.00426. 2001 Siddiqui, J., Phillips, A. L., Freedland, E. S., Sklar, A. R., Darkow, T., & Harley, C. R. (2009). Prevalence and cost of HIV-associated weight loss in a managed care population. Current Medical Research and Opinion, 25, 1307-1317. http://dx.doi.org/10.1185/03007990902902119 Smit, E., Skolasky, R. L., Dobs, A. S., Calhoun, B. C., Visscher, B. R., Palella, F. J., & Jacobson, L. P. (2002). Changes in the incidence and predictors of wasting syndrome related to human immunodeficiency virus infection, 1987-1999. American Journal of Epidemiology, 156(3), 211-218. http:// dx.doi.org/10.1093/aje/kwf039 Struwe, M., Kaempfer, S. H., Geiger, C. J., Pavia, A. T., Plasse, T. F., Shepard, K. V., . Evans, T. G. (1993). Effect of dronabinol on nutritional status in HIV infection. Annals of Pharmacotherapy, 27(7-8), 827-831. Tang, A., Jacobson, D., Spiegelman, D., Knox, T., & Wanke, C. (2005). Increasing risk of 5% or greater unintentional weight loss in a cohort of HIV-infected patients, 19952003. Journal of Acquired Immune Deficiency Syndrome, 40, 70-76. Wallis, R. S., Nsubuga, P., Whalen, C., Mugerwa, R. D., Okwera, A., Oette, D., . Ellner, J. J. (1996). Pentoxifylline therapy in human immunodeficiency virus-seropositive persons with tuberculosis: A randomized, controlled trial. Journal of Infectious Diseases, 174(4), 727-733. http://dx.doi.org/ 10.1093/infdis/174.4.727 Von Roenn, J. H., Armstrong, D., Kotler, D. P., Cohn, D. L., Klimas, N. G., . Weitzman, S. A. (1994). Megestrol acetate in patients with AIDS-related cachexia. Annals of Internal Medicine, 15(121), 393-399.
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Yaresheski, K., Tebas, P., Stanerson, B., Claxton, S., Martin, D., Bae, K., . Powderly, W. G. (2001). Resistance exercise training reduces hypertriglyceridemia in HIV-infected men treated with antiviral therapy. Journal of Applied Physiology, 90(1), 133-138.
In 1987, the Centers for Disease Control and Prevention (Centers for Disease Control and Prevention, 1987) defined HIV wasting syndrome as the involuntary loss of greater than 10% of body weight accompanied by chronic diarrhea, weakness, or fever for 30 days or more in the absence of concurrent illness. Since effective antiretroviral therapy (ART) has become available, several other definitions have been proposed (Mangili, Murman, Zampini, & Wanke, 2006; Polsky, Kotler, & Steinhart, 2001), which generally incorporate one or more of the following criteria: (a) unintentional weight loss of more than 5%–10%, (b) body mass index (BMI) less than 20, and (c) body cell mass loss of more than 5%. In clinical practice, HIV-associated
wasting is usually defined as any unintentional weight loss, characterized by loss of muscle mass in men and a loss of both muscle and fat mass in women, which is predictive of disease progression and mortality (Kotler, Wang, & Pierson, 1985; Siddiqui et al., 2009; Tang, Jacobson, Spiegelman, Knox, & Wanke, 2005).
Prevalence The prevalence of HIV-associated wasting was estimated at 30% during the pre-ART era of the HIV epidemic (Nahlen et al., 1993; Smit et al., 2002). While the prevalence has declined, wasting still occurs, especially in injection drug users (IDUs) and individuals with food insecurity, high viral loads, and low-income levels (,$500/month; Campa et al., 2005; Mangili et al., 2006; Siddiqui et al., 2009). A number of factors influence wasting prevalence, including reduced food intake, malabsorption, endocrine abnormalities, metabolic disorders, and virologic and immune factors (Campa et al., 2005; Dudgeon et al., 2006; Grunfeld et al., 1992).
Assessment and Clinical Measurement Tools Optimal nutrition status supports optimal immune function (Campa et al., 2005). There are many approaches to nutrition status assessment, including the ABCD approach that incorporates Joyce K. Keithley, DNSc, RN, FAAN, is a Professor at Rush University College of Nursing, Chicago, Illinois. Barbara Swanson, PhD, RN, FAAN, is a Professor at Rush University College of Nursing, Chicago, Illinois, USA.
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anthropometric, biochemical, clinical, and dietary measures. A summary of key parameters within each of these measures can be found in Table 1. A nutrition status assessment should be performed two to three times per year to identify individuals who are at risk for, or have, wasting (Polsky et al., 2001). Anthropometric measures include the evaluation of height, weight, and body composition. An unintentional weight loss of greater than 5%–10% over any time frame is considered clinically significant (Mangili et al., 2006; Polsky et al., 2001). BMI, a marker of optimal weight for height, is calculated from weight in kilograms/height in meters squared. Automatic BMI calculators are available online for easy calculation. A BMI lower than 20 in association with loss of lean body mass (LBM) is indicative of wasting (Mangili et al., 2006; Polsky et al., 2001). Body composition measures assess body fat and muscle distribution and can be measured using bioelectrical impedance analysis and triceps skinfold and waist and hip circumferences (Table 1). Measures lower than 90%–95% of normal are indicative of wasting (Kotler et al., 1985; Polsky et al., 2001). Biochemical assessment includes nutrition-related laboratory parameters such as hemoglobin and blood glucose (Table 1). Deficiencies may contribute to the wasting process and may adversely affect immune function (Campa et al., 2005). The clinical history and physical examination collect information about health problems that may contribute to wasting, such as drug-nutrient interactions (Table 2) and physical signs of wasting, such as loss of subcutaneous fat and muscle wasting. Several methods for collecting the dietary history are available, including 24-hour recall, food frequency questionnaire, food diaries, and direct observation. The 24-hour recall is the quickest and most widely used technique, although all techniques provide useful information. As part of the dietary history, it is also important to assess food intolerances and nutrition-related factors and symptoms, such as anorexia and depression. A variety of tools are available for determining nutrition status. One tool adapted and tested specifically for use in persons living with HIV infection (PLWH) is the Subjective Global Assessment for HIV-Infected Individuals (SGA-HIV; Bowers & Dols, 1996). An overall SGA-HIV rating can be made based on data easily obtained from the medical
Table 1.
Anthropometric, General Health, and Dietary Assessment Measures
Anthropometric measures Height, weight, body mass index (BMI) Bioelectrical impedance analysis (BIA): body cell mass (BCM), fat mass, body water Triceps skinfold, waist and hip circumference Biochemical measures (nutrition-related) Hemoglobin/hematocrit Total protein, albumin, liver, and renal function Fasting blood glucose and lipids Clinical history and examination Medications that impact nutrition Gastrointestinal co-morbidities Endocrine co-morbidities Secondary infections, such as thrush Dietary history Usual dietary intake and patterns Estimated energy intake Food allergies/intolerances/restrictions, use of dietary supplements Factors & symptoms that affect intake (e.g., poor appetite, fatigue, substance abuse, food insecurity, depression, inadequate nutrition knowledge)
history and physical examination (Figure 1). Individuals who are mildly-to-moderately malnourished or severely malnourished require additional followup by nurses, dietitians, and other members of the health care team to address nutrition-related issues.
What Interventions are Effective for Preventing and Treating Wasting in PLWH? Recommended for Practice Indications for nutrition intervention. Nutrition intervention is indicated for: (a) significant weight loss (.5% in 3 months), (b) significant body cell mass loss (.5% in 3 months), and (c) BMI lower than 18.5 kg/m2. Recommended protein intake is 1.25–1.5 g/kg of body weight; recommended energy intake (calories from protein, carbohydrate, and fat) is 25 kcal/kg of body weight (Ockenga et al., 2006). Clinical guidelines established by the European Society for Parenteral and Enteral Nutrition (Ockenga et al., 2006) identified indications for nutrient intervention, as well as recommendations for protein and overall energy intake. When significant weight loss, significant body cell mass depletion,
Keithley, Swanson / Wasting Table 2.
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Antiretroviral Medication Administration: Recommended Food Intake Drug
Multi-class combination agents Efavirenz/emtricitabine/tenofovir (AtriplaÒ) Emtricitabine/rilpivirine/tenofovir (CompleraÒ) Nucleoside reverse transcriptase inhibitors Lamivudine/zidovudine (CombivirÒ) Emtricitabine (EmtrivaÒ) Lamivudine (EpivirÒ) Abacavir/lamivudine (EpzicomÒ) Zidovudine (RetrovirÒ) Abacavir/lamivudine/zidovudine (TrizivirÒ) Tenofovir/emtricitabine (TruvadaÒ) Didanosine (VidexÒ) Tenofovir (VireadÒ) Stavudine (ZeritÒ) Abacavir (ZiagenÒ) Nonnucleoside reverse transcriptase inhibitors Rilpivirine (EdurantÒ) Etravirine (IntelenceÒ) Delavirdine (RescriptorÒ) Efavirenz (SustivaÒ) Nevirapine (ViramuneÒ) Protease inhibitors Amprenavir (AgeneraseÒ) Tipranavir (AptivusÒ) Indinavir (CrixivanÒ) Saquinavir (InviraseÒ) Lopinavir/ritonavir (KaletraÒ) Fosamprenavir (LexivaÒ) Darunavir (PrezistaÒ) Atazanavir (ReyatazÒ) Nelfinavir (ViraceptÒ) Entry inhibitor Maraviroc (SelzentryÒ) Integrase inhibitor Raltegravir (IsentressÒ)
Administration Recommendation Take with food Take on an empty stomach May be taken with or without food May be taken with or without food May be taken with or without food May be taken with or without food May be taken with or without food May be taken with or without food May be taken with or without food Take on an empty stomach May be taken with or without food May be taken with or without food May be taken with or without food Take with food Take after eating a meal May be taken with or without food Take on an empty stomach May be taken with or without food May be taken with or without food; do not take with a high fat meal May be taken with or without food Take without food or with a light meal; drink at least 48 oz of fluids/day to prevent kidney stones Take within 2 hours of a full meal May be taken with or without food May be taken with or without food Take with food Take with food Take with food May be taken with or without food May be taken with or without food
and low BMI occur, nutrition intervention that focuses on maximizing food intake is recommended. Meals should incorporate individual preferences and high calorie/high protein foods such as cheese and peanut butter. The European Society for Parenteral and Enteral Nutrition guidelines were based on a review of relevant publications since 1985, as well as interdisciplinary group expert opinion. Likely to be Effective Nutrition counseling. In disease-related wasting, nutrition counseling with or without oral nutritional
supplements may improve body weight, composition, and grip strength, an early indicator of nutritional status. Areas of nutrition counseling include the importance of maintaining body weight and eating nutritious foods (i.e., foods rich in protein, calories, vitamins, minerals), preventing drug-nutrient interactions (Table 2), and managing nutrition-related symptoms and barriers, such as lack of appetite and living in a food desert (Polsky et al., 2001). In a meta-analysis of 45 clinical trials, Baldwin and Weekes (2011) suggested that nutrition counseling with or without oral nutrition supplements significantly improved weight gain (11.47–3.75
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Patient Name:________________________
Patient ID:______________
Date:___________
Part 1: Medical History 1. Weight Change A. Overall change in past 6 months: __________kgs B. Percent change: __________Gain - <5% loss __________5%-10% loss __________>10% loss C. Change in past 2 weeks: __________Increase __________No change __________Decrease D. Height________; Weight_______ Weight 6 mo ago: __________ Weight 12 mo ago: __________ 2. Dietary Intake A. Overall change: __________No change; _________Change _________ B. Type of change: __________ More: _________ Less: __________Much less __________ Suboptimal solid diet _________ Hypocaloric liquids __________ Full liquid diet __________Starvation C. Duration: __________Weeks 3. Gastrointestinal Symptoms (persisting for >2 weeks) _________None; _________Nausea; ________Vomiting; ________Diarrhea; _________Anorexia; ________Constipation; _________Oral sores; _________Dysphagia; _________Taste changes 4. Functional Impairment (nutritionally related) A. Overall impairment: _________None (no limitations) ________ Mild (not normal self; able to do fairly normal activities) ________ Moderate (not up to most things; > ½ day in bed/chair) _________Severe (primarily bedridden) B. Change in past 2 weeks: _________ Improved _________ No Change _________ Regressed Part 2: Physical Examination 5. Evidence of: Loss of subcutaneous fat Muscle wasting Edema Ascites (renal/ hepatic)
____Normal;____ Mild; ____Moderate; ____Severe ____Normal; ____Mild; ____ Moderate; ____Severe ____Normal; ____Mild; ____ Moderate; ____Severe ____Normal; ____Mild; ____Moderate; ____Severe
Part 3: SGA Rating (check one) A. A. Well-nourished B. Mild to moderately malnourished C. Severely malnourished Figure 1. Revised subjective global assessment for HIV-infected individuals. From: Bowers, J. M., & Dols, C. L. (1996). Subjective Global Assessment in HIV-infected patients. Journal of the Association of Nurses in AIDS Care, 7(4). 83–89. http://dx.doi. org/10.1016/S1055-3290(96)80062-8. Republished with permission from Elsevier Inc.
kg), triceps skinfold thickness (1.40–1.22 mm), midarm muscle circumference (.81–.89 mm), and hand grip strength (11.67 kg). Qualified nutrition counseling can be provided by registered dietitians, die-
tetic technicians, and other health care professionals with specialized training in nutrition. Oral supplements are available in the form of drinks, candy bars, and soups that are tasty and easy to use,
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including specialized products for patients with specific intolerances (e.g., lactose intolerance, fat malabsorption). Studies in the meta-analysis were of low-to-moderate quality, with varied interventions and patient groups (Baldwin & Weekes, 2011). No evidence of survival benefits related to nutrition counseling with or without oral nutritional supplements was found, and a lack of evidence related to effects on quality of life and functional status was reported. Anabolic/androgenic agents. Anabolic steroids have been associated with gains in weight and lean body mass, as well as improvements in parameters of physical performance. No adverse effects on viral replication have been reported. In men, treatment with testosterone is associated with increased fat and lean body mass, but increased fat mass only in women (Looby, Collins, Lee, & Grinspoon, 2009; Moyle et al., 2004). Anabolic/androgenic agents have been used to promote weight gain, especially LBM. A metaanalysis of 18 studies concluded that recombinant human growth hormone, anabolic steroids, and testosterone were equally efficacious in increasing LBM in HIV-related wasting (DEXA-measured mean LBM gain 5 2.74–3.3 kg; Looby et al., 2009). Treatment with recombinant human growth hormone may confer the additional benefit of improving functional performance and quality of life (Moyle et al., 2004). There is some evidence for gender-specific effects. In men, short-term treatment with testosterone (12 weeks) was associated with increased fat and LBM, but testosterone increased fat mass (12 kg) only in women. In women with low testosterone levels, however, long-term testosterone treatment (18 months) increased lean mass (11.8 kg) and had no effect on fat mass (Looby et al., 2009). Although anabolic/androgenic agents are likely effective for the management of HIV-associated wasting, the gains in LBM were found to be small and of questionable clinical relevance. Moreover, methodological limitations of the extant literature have precluded advancing treatment recommendations. These limitations included short treatment durations, different formulations of study drug, inadequate statistical power to test a range of doses, non-
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standardized operational definitions of wasting, and nonequivalent measures of body composition (Looby et al., 2009; Moyle et al., 2004). Exercise. Early concerns about the safety of aerobic exercise on virological and immune outcomes have been discredited. A meta-analysis of 14 studies concluded that aerobic and resistive exercise, both alone and in combination, were associated with increased muscle mass (1.1 to 6.9 kg) and improvements in cardiovascular fitness and depression; improvements were contingent upon adhering to an activity regimen for a minimum of 20 minutes/day, 3 days/week for 5 weeks. No deleterious immunological or virological effects were found (O’Brien, Nixon, Tynan, & Glazier, 2010). Resistive exercise alone for 16 weeks has been shown to increase LBM and muscle strength and to reduce serum triglycerides (Yaresheski et al., 2001). Persistent adherence to aerobic and/or resistive exercise is a safe and effective approach for favorably modulating body composition and metabolic parameters in HIV-associated wasting. Effectiveness Not Established Macronutrient supplementation. In a metaanalysis of eight randomized controlled trials (Mahlungulu, Grobler, Visser, & Volmink, 2007), macronutrient supplementation significantly improved overall calorie (1367 kcal/day) and protein intake (117 g/day) compared with individuals who did not receive supplementation. However, no effect on weight, fat mass, or fat-free mass was noted. Studies in this review were limited by small sample sizes, relatively high attrition rates, and differences in macronutrient supplements and HIV disease stage. Effects of balanced nutritional supplements on disease progression and survival are equivocal at this time. Herbal supplements. No published meta-analysis or integrative reviews were found specific to the safety and efficacy of herbal supplements to combat wasting in HIV disease. A recent study found that herbal supplement use was infrequent in PLWH, and that the most commonly used dietary supplements were vitamins, calcium, and omega-3 fatty acids (Aghdassi, Bondhar, Salit, Tinmouth, & Allard, 2009).
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Appetite stimulants. Megestrol acetate (MA, Megace ESÒ; Strativa Pharmaceuticals, Woodcliff Lake, NJ) is U.S. Food and Drug Administration (FDA)-approved to manage HIV-associated weight loss. Evidence has suggested that most of the weight gain is in the form of fat mass, possibly due to the hypogonadic effect of MA that favors gain of fat mass over lean mass (Oster et al., 1994; Von Roenn et al., 1994), and co-administration of testosterone does not increase LBM (Mulligan et al., 2007). The recommended dosage is 625 mg/day and the durability of weight gain once MA is discontinued is unknown. Interactions with certain antiretroviral medications have been reported. Co-administration of etravirine has been associated with slight increases in plasma estradiol, while decreased plasma concentrations of estradiol and progestin have been observed with co-administration of efavirenz and nevirapine, both of which are known inducers of CYP3A4. The latter may potentially affect the efficacy of oral contraceptives. A recent systematic review concluded that the lack of rigorous studies in PLWH precludes recommendations for the use of MA to manage HIV-related wasting (Berenstein & Ortiz, 2005). Dronabinol is FDA-approved to manage HIVassociated anorexia. The recommended dosage is 2.5 mg twice a day. Limited data have shown mixed findings related to appetite improvement and no evidence for weight gain (Beal et al., 1995; Oster et al., 1994; Struwe et al., 1993). Long-term use (12 months) has been associated with stable body weight in late-stage AIDS patients, but 44% of study participants showed expected, non-life-threatening, adverse central nervous system effects (Beal et al., 1997). Effectiveness Unlikely Micronutrient supplementation. Vitamin A, vitamin D, and zinc supplements have not been associated with reversal of wasting in HIV disease. A meta-analysis of six vitamin A clinical trials, one vitamin D clinical trial, two zinc clinical trials, three selenium clinical trials, and 10 multiple supplement trials in adults revealed no effect of any of these vitamins or minerals on wasting (Irlam, Visser, Rollins, & Siegfried, 2010). Limited evidence suggested that selenium supplements could be associated with
reductions in viral load, and equivocal evidence suggested that multiple supplements were associated with enhanced cellular immunity. Studies included in the meta-analysis varied in methodological quality, especially in terms of incomplete outcome reporting, selective reporting, and other biases. Cytokine modulators. Because HIV-associated wasting has been linked to overproduction of inflammatory cytokines (Rivera et al., 2001; Roubenoff et al., 2002), cytokine suppressors have been investigated for their ability to restore LBM. In a randomized, placebo-controlled trial, an 8-week course of thalidomide at a dose of 100 or 200 mg/day was associated with modest weight gains of 2.2 and 1.5 kg, respectively, but it also increased plasma concentrations of HIV RNA (Kaplan et al., 2000). In a clinical trial of thalidomide to manage aphthous ulcers, participants in the treatment group showed increases in plasma concentrations of HIV RNA and tumor necrosis factor-a. Trials of other cytokine modulators, including omega-3 fatty acids (Hellerstein et al., 1996) and pentoxifylline (Wallis et al., 1996), have shown no effects for weight or LBM gain.
Case Study Case Description DT is a 26-year-old white man who presents to a municipal infectious disease clinic with a 3-month history of weight loss. Diagnosed with HIV infection 6 years ago, DT lives in a homeless shelter, has a history of IDU, and drinks 2–3 beers/day. Baseline nutrition assessment reveals: height, 5 feet 8 inches; medium frame size; current weight 120 pounds, compared to a usual weight of 140 pounds; and a BMI of 18. Bioelectrical impedance analysis indicates mild dehydration and body cell mass depletion. His dietary intake for the past month was approximately 1,000 kcal/day and consisted primarily of carbonated beverages and fast foods. His estimated resting energy expenditure is 2,200 kcal/day. DT states that he does not have a reliable food source and does not always remember to take his ART medications. Laboratory findings include: viral load . 100,000 copies/mL, CD4 1 T-cell count equals 225 cells/mm3,
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and hemoglobin equals 12.1 g/dL. DT denies a recent history of diarrhea or secondary infections. Recommended for Practice DT meets all of the indications for nutrition intervention, including significant weight loss over the previous 3 months (20 pounds or 14% loss), body cell mass depletion, and a BMI , 18.5 kg/m2. Nutrition interventions that provide 1.25–1.5 grams protein/kg of body weight and 25 kcal/kg of body weight are recommended. Likely to be Effective Initial visit. Complete nutrition assessment using SGA-HIV and ABCD assessment guides to identify wasting etiologies and nutrition-related problems and barriers are warranted. It will help to collaborate with the dietitian, case manager, and social worker to conduct the initial assessment and develop strategies to improve nutrition intake and weight gain, taking into consideration DT’s lifestyle and resources. It is important to provide nutrition counseling and specific options for a steady food source of high-protein and high-calorie meals, including oral nutritional supplements. Options might include specific meal arrangements with the homeless shelter and programs that provide free oral nutritional supplements. 1-month follow-up. The nurse should assess for any changes in nutritional status, focusing on body weight, laboratory parameters, and any new nutrition problems or barriers. If no improvement is noted, screen for undiagnosed wasting etiologies, such as oral lesions, nausea, and pain. Evaluate effectiveness of meal options and use of supplements. Consider aerobic exercise with or without resistive exercise to improve body cell mass. 3-month follow-up. Use assessments and interventions as noted above and adjust plan based on changes in nutritional status. A weight gain of 1–2 pounds/month or 3–6 pounds/3 months is a realistic goal. Collaborate with DT and his health care team members, case manager, and others to develop strategies to address IDU, adherence, homelessness, and other issues.
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DT’s homelessness and IDU present significant challenges to combating wasting. Based on current evidence and guidelines, DT meets indications for nutrition intervention. Nutrition counseling, oral nutrition supplements, anabolic/androgenic agents, and exercise are likely to be effective in wasting reversal. Because effectiveness is either not established or unlikely, herbal supplements, macronutrient and micronutrient supplements, cytokine modulators, and appetite stimulants are not recommended. As an initial plan, reliable meal sources and oral nutrition supplements are provided. At his 1-month followup visit, DT reported adherence to the meal options and had gained 2 pounds using the meal and oral nutrition supplement options provided. At his 3-month visit, weight gain continued at a rate of 1– 2 pounds/month. The health care team recommended that DT continue on the same nutrition plan and consider exercise to promote lean body mass gain.
Clinical Considerations Wasting remains a common problem in HIVinfected individuals, especially among injection drug users and those who live below the poverty line, have food insecurity, and have high viral loads. Assessment of nutrition status using valid and reliable tools at regular intervals is the first step in combating HIV-associated wasting. Current evidence and guidelines support the use of nutrition counseling, oral nutrition supplements, anabolic/androgenic agents, and exercise as likely to be effective in wasting reversal. Effectiveness has not been established or is unlikely for herbal supplements, macronutrient and micronutrient supplements, cytokine modulators, and appetite stimulants at this time.
Disclosures The authors report no real or perceived vested interests that relate to this article (including relationships
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with pharmaceutical companies, biomedical device manufacturers, grantors, or other entities whose products or services are related to topics covered in this manuscript) that could be construed as a conflict of interest.
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