A.S.P.E.N. Clinical Guidelines: Nutrition Support of Children With Human Immunodeficiency Virus Infection

The clinical characteristics of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) in children differ substantially from those in adults, and these differences are important to consider in providing both medical and nutrition care. Growth failure, wasting, and loss of active lean tissue are all associated with increased mortality and accelerated disease progression. The use of highly active antiretroviral therapy (HAART) has improved the prognosis and life span of children infected with HIV (HIV+) and has reduced rates of wasting. However, the emergenceof HIV-associated lipodystrophy (HIVLD) has emphasized the extensive nutrition and metabolic manifestations of HIV infection. Maintaining the nutrition status of the HIV+ child is therefore crucial for optimal health outcomes. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) is an organization comprised of healthcare professionals representing the disciplines of medicine, nursing, pharmacy, dietetics, and nutrition science. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of nutrition support therapy. A.S.P.E.N. vigorously works to support quality patient care, education, and research in the fields of nutrition and metabolic support in all healthcare settings. These clinical guidelines were developed under the guidance of the A.S.P.E.N. Board of Directors. Promotion of safe and effective patient care by nutrition support practitioners is a critical role of the A.S.P.E.N. organization. The A.S.P.E.N. Board of Directors has been publishing clinical guidelines since 1986.1-3 Starting in 2007, A.S.P.E.N. has revised these clinical guidelines on an ongoing basis, reviewing about 20% of the chapters each year in order to keep them as current as possible. These A.S.P.E.N. Clinical Guidelines are based upon general conclusions of health professionals who, in developing such guidelines, have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy. However, the professional judgment of the attending health professional is the primary component of quality medical care. Because guidelines cannot account for every variation in circumstances, practitioners must always exercise professional judgment in their application. These Clinical Guidelines are intended to supplement but not replace professional training and judgment. These clinical guidelines were created in accordance with Institute of Medicine recommendations as “systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances.”4 These clinical guidelines are for use by healthcare professionals who provide nutrition support services and offer clinical advice for managing adult and pediatric (including adolescent) patients in inpatient and outpatient (ambulatory, home, and specialized care) settings. The utility of the clinical guidelines is attested to by the frequent citation of these documents in peer-reviewed publications and their frequent use by A.S.P.E.N. members and other healthcare professionals in clinical practice, academia, research, and industry. They guide professional clinical activities, they are helpful as educational tools, and they influence institutional practices and resource allocation.5 These clinical guidelines are formatted to promote the ability of the end user of the document to understand the strength of the literature used to grade each recommendation. Each guideline recommendation is presented as a clinically applicable statement of care and should help the reader make the best patient-care decision. The best available literature was obtained and carefully reviewed. Chapter author(s) completed a thorough literature review using MEDLINE®, the Cochrane Central Registry of Controlled Trials, the Cochrane Database of Systematic Reviews, and other appropriate reference sources. These results of the literature search and review formed the basis of an evidence-based approach to the clinical guidelines. Chapter editors work with authors to ensure compliance with the author's directives regarding content and format. Then the initial draft is reviewed internally to ensure consistency with the other A.S.P.E.N. Guidelines and Standards and reviewed externally (either by experts in the field within our organization and/or outside of our organization) for appropriateness of content. The final draft is then reviewed and approved by the A.S.P.E.N. Board of Directors. The system used to categorize the level of evidence for each study or article used in the rationale of the guideline statement and to grade the guideline recommendation is outlined in Table 1.6 The grade of a guideline is based on the levels of evidence of the studies used to support the guideline. A randomized controlled trial (RCT), especially one that is double-blind in design, is considered to be the strongest level of evidence to support decisions regarding a therapeutic intervention in clinical medicine.7 A systematic review (SR) is a specialized type of literature review that analyzes the results of several RCTs. A high-quality SR usually begins with a clinical question and a protocol that addresses the methodology to answer this question. These methods usually state how the literature is identified and assessed for quality, what data are extracted, how they are analyzed, and whether there were any deviations from the protocol during the course of the study. In most instances, meta-analysis (MA), a mathematical tool to combine data from several sources, is used to analyze the data. However, not all SRs use MA. A level of I, the highest level, will be given to large RCTs where results are clear and the risk of alpha and beta error is low (well-powered). A level of II will be given to RCTs that include a relatively low number of patients or are at moderate to high risk for alpha and beta error (underpowered). A level of III is given to cohort studies with contemporaneous controls or validation studies, while cohort studies with historic controls will receive a level of IV. Case series, uncontrolled studies, and articles based on expert opinion alone will receive a level of V. Table 2 provides the entire set of guideline recommendations for nutrition support in children infected with HIV. 1. Nutrition assessment of children who are HIV+ should be performed at baseline and serially. (Grade: D) Rationale: Growth failure is common in children who are HIV+ and is associated with greater mortality risk. While birth weights and gestational ages are not different among children who are HIV+ and uninfected (HIV–), by age 3 months8,9 and up to 5 years,10 children who are HIV+ have lower weight and height. In fact, wasting syndrome is among the Centers for Disease Control and Prevention (CDC) criteria used to categorize children in clinical category C (severely symptomatic)11 (Table 3). Clinical and laboratory factors associated with this malnutrition include history of pneumonia, maternal illicit drug use during pregnancy, lower infant CD4 count, and increased HIV-1 RNA viral load.10 Decreased nutrient intake, increased energy requirement, malabsorption, and psychosocial issues may all contribute to undernutrition in the pediatric HIV population. Growth failure is a prognostic indicator of mortality in pediatric HIV infection.12-14 See Tables 3 and 4. 2. Anthropometry and body composition studies should be performed. (Grade: E) Rationale: Children with HIV infection can have a significant loss of lean body mass, even in the absence of weight loss.18 Weight in children who are HIV+ can be misleading, since fluid shifts caused by vomiting, diarrhea, and altered fluid status can transiently alter the measured weight. Additionally, body mass changes associated with HIV wasting such as preferential loss of fat, loss of lean body mass, and changes in body composition due to HIVLD may not be adequately assessed without body composition evaluation. Anthropometric measures, including mid–arm muscle area, subscapular skinfold, and triceps skinfold, can better reflect fat and lean body mass compared with weight and height measurements alone. Quantification of lean and fat mass is of special importance in these patients due to the increasing incidence of lipodystrophy. See Table 5. 3. Oral nutritional supplements or enteral tube feedings may improve weight and growth in children who are HIV+ with growth failure. (Grade: C) Rationale: When the nutrition assessment indicates that a child fails to meet growth standards, nutritional supplements have restored weight and growth in some children.22 If oral interventions fail, enteral tube feeding improves weight gain in children with growth failure.23,24 In the circumstance of severe malnutrition, nutrition therapy with an elemental diet may be more effective than higher caloric intake of a standard formula for weight gain.25 Accurate energy and protein requirements for children who are HIV+ have not yet been established. See Table 6. 4. Antiretroviral therapy improves growth in children who are HIV+. (Grade: E) Rationale: Children born to mothers who are HIV+ in both developing and developed countries have lower weight and height z scores from birth to at least 5 years of age.15,21 Growth failure is a prognostic indicator of mortality in pediatric HIV infection.12-14 The incidence of wasting has fallen since the implementation of HAART; however, multiple factors continue to contribute to growth failure. Children with a virologic response (those who reach HIV viral load <400 or 500 copies/mL) or have significant reduction (>1.5 log) in viral load to therapy tend to have a greater increase in weight and height compared with virologic nonresponders.16,26 HAART therapy has been shown to increase weight- and height-for-age, while body mass index (BMI) remains unchanged.16,26 See Table 7. 5. Children with HIV lipodystrophy should have laboratory evaluation and clinical management of hypertriglyceridemia and hypercholesterolemia. (Grade: D) Rationale: While initiation of HAART includes many benefits, it has transformed HIV into a chronic disease with the increased risk of metabolic complications. HIVLD has 3 main components: abnormal blood lipid profiles (hypertriglyceridemia and hypercholesterolemia), insulin resistance, and body fat redistribution.30 Children and adolescents who are HIV+ may exhibit features of lipohypertrophy, lipoatrophy, or a combination of the 2. Lack of consensus of the definition of HIVLD has made its characterization difficult. Moreover, signs of HIVLD are more difficult to identify in children and adolescents than in adults because of subtle fat redistribution and physical changes during puberty. Estimates of the prevalence of HIVLD in children and adolescents range from 13% to 67%.19,27,30-34 The development of symptoms has been linked to protease inhibitor (PI) therapy,33-35 duration of HAART therapy,30,33 nucleoside analog–containing regimens, and increasing doses of medications.36 There is increased association of HIVLD with puberty33,37 and female gender.30 Management of lipodystrophy complications in children who are HIV+ has not been well studied. See Table 8. 6. Supplementation with multivitamins should be provided to pregnant and lactating women who are HIV+. (Grade: B) Rationale: Supplementation with standard pregnancy multivitamins in pregnant and lactating women in the developing world has been associated with improved fetal and childhood outcomes in 1 large randomized control trial.39-42 In this trial, multivitamin supplementation was shown to improve infant outcomes (eg, decrease prematurity, increase birth weight, decrease the incidence of small gestational age infants) and to improve childhood outcomes (higher CD4 counts, decreased diarrhea, and improved development).39-42 Another trial investigated the effects of zinc supplementation vs placebo on pregnant women and found no adverse effects on woman or infants compared with pregnant mothers who received placebo.43 Because of its recognized modulation of the immune system, supplemental vitamin A was investigated in pregnant women who are HIV+. While some trials found improved infant outcomes (Table 9), 2 large trials suggested an increased rate of mother-to-child HIV transmission in a subset of the population with high-dose supplemental vitamin A,44,45 while other smaller trials found no effect.46,47 High-dose vitamin A supplementation in HIV+ mothers is not currently recommended, since it does not reduce47-49 and may increase mother-to-child HIV transmission.44 See Table 9. 7. Micronutrient supplementation should be considered in children who are HIV+. (Grade: C) Rationale: The micronutrient status of children who are HIV+ continues to be an area of intense research. Supplementation of multivitamins and micronutrients, at the required dietary allowance dosage, may be indicated in children who are HIV+. In the United States, children who are HIV+ may have reduced dietary intake of vitamin E,51 calcium, and vitamin D.52 Consumption of a multivitamin is associated with better bone mineral density in children who are HIV+.52 Selenium deficiency has been linked with increased mortality risk in children who are HIV+.53 The majority of research to date has been conducted in developing countries where micronutrient deficiencies are common regardless of HIV status, making it difficult to differentiate the etiology of nutrient deficiencies secondary to HIV/AIDS or background rates of micronutrient malnutrition. In 1 study, vitamin A supplementation in children who are HIV+ was shown to decrease diarrhea, upper respiratory tract infections, and mortality.54,55 In another study, zinc supplementation was associated with no change in respiratory tract infection, CD4 counts, or HIV viral load, but it decreased diarrhea illness in children who are HIV+.56 See Table 10. 8. Women who are HIV+ in resource-rich settings are advised to formula feed exclusively, while in resource-poor settings, exclusive breastfeeding is recommended. (Grade: B) Rationale: HIV transmission through breastfeeding may account for as much as 12%–16% of postnatal transmission.59-61 In developed countries, it is recommended that mothers who are HIV+ exclusively formula feed to avoid the risk of HIV transmission.62 In resource-poor settings, the practical aspects of implementation of formula feeding may be difficult due to unsafe water, lack of availability of milk substitutes, varying cultural norms, and risk of maternal stigmatization.62 Maternal characteristics that place infants at increased risk for HIV transmission include higher plasma and milk HIV viral load, mastitis, and decreased maternal CD4 count.62 Furthermore, the protective factors of breastfeeding in these environments may include decreased diarrheal illness and decreased mortality. The World Health Organization recommends that when replacement feeding is feasible, acceptable, affordable, sustainable, and safe, then avoidance of breastfeeding by women who are HIV+ is recommended.63 Otherwise, in the developing world, the morbidity and mortality of infants born to mothers who are HIV+, whether exclusively fed breast milk or formula, may be equivocal.64,65,66 Should breastfeeding be selected, exclusive breastfeeding is advised, as it is associated with decreased vertical transmission and infant mortality compared with mixed feeding regimens.60,67 Furthermore, a 6-month period of exclusive breastfeeding may be recommended, as the risk of transmission significantly increases with time.67 Peripartum maternal and infant antiretroviral prophylaxis during breastfeeding may also decrease the risk of HIV transmission to the infant postnatally. See Table 11.