Nutrition and HIV/AIDS

New York State Department of Health AIDS Institute Nutrition and HIV/AIDS Peter Wasserman, RD, MA Metabolic Support, Infectious Disease Division, Department of Medicine, New York Hospital Queens, Flushing, NY Sorana Segal-Maurer, MD Attending Physician, Infectious Disease Division, Department of Medicine, New York Hospital Queens, Flushing, NY Associate Professor of Clinical Medicine, Weill Medical College of Cornell University, New York, NY David S. Rubin, MD Medical Director, AIDS Designated Center, Attending Physician, Infectious Disease Division, Department of Medicine, New York Hospital Queens, Flushing, NY Clinical Assistant Professor of Medicine, Weill Medical College of Cornell University, New York, NY

The Implications of HIV on Nutrition • In New York State over 35% of persons living with HIV infection are over 50 years old and 38% are between the ages of 40 and 49 years old. Seventy percent of persons living with HIV/AIDS are men and 57% of new cases occur in men who have sex with men.1 This demographic has broad implications for the nutritional care of persons with HIV infection. • Wasting disease was the prominent nutritional issue in patient management prior to the advent of antiretroviral therapy (ART). Although wasting disease still occurs, HIV infection has become a chronic disease for most patients. • Increasingly, newly diagnosed persons with HIV/AIDS live in urban poverty areas and experience food and housing insecurity, as well as limited access to fresh food stuffs.2,3 New York State Department of Health AIDS Institute

Key Point Comorbidities including cardiovascular disease, osteopenia/osteoporosis, and sarcopenia are now predominant in HIV infection, have a significant dietary component, and are associated with aging. New York State Department of Health AIDS Institute

Multicausation Model of Malnutrition New York State Department of Health AIDS Institute

Manifestations of Malnutrition Malnutrition may manifest as overnutrition, undernutrition, or single nutrient deficiency. It can occur in association with: • Food insecurity • Poor-quality, calorie-dense diet • Loss of perception of hunger or appetite • Malabsorption • Altered metabolism • Sedentary lifestyle New York State Department of Health AIDS Institute

Food Insecurity Recommendation: Advise patients of organizations in their area offering congregate meals, home meal delivery, and/or food pantries. (AIII) • Food insecurity is defined as limited or uncertain availability of nutritionally adequate, safe foods or the inability to acquire personally acceptable foods in socially acceptable ways.4 • Food insecurity may exist with or without hunger and may contribute to wasting or obesity.5 • Association with obesity, while counterintuitive, is likely due to reliance on inexpensive calorie-dense convenience foods, fast food or take-out food, and sugar-sweetened beverage intake.6 New York State Department of Health AIDS Institute

Key Point The United States Department Agriculture food security questionnaire (six-question short-form) may be used to assess household food security.7 The questionnaire is available at: http://www.ers.usda.gov/Publications/err108/err108.pdf New York State Department of Health AIDS Institute

Poor-Quality, Calorie-Dense Diet Recommendation: Ascertain where patients shop for food and ingredients used in meal preparation and counsel as needed. (AIII) • Dietary intake high in refined white flour, polished (white or yellow) rice, sugar, sugar-sweetened beverages, saturated and polyunsaturated fat, and salt is strongly associated with hyperlipidemia and insulin resistance in HIV-infected persons.8-10 • Patient diet is likely associated with the large interindividual variability in lipid response to specific antiretrovirals.8 New York State Department of Health AIDS Institute

Appetite/Hunger Suppression Febrile response to opportunistic or secondary infection, oropharyngeal or esophageal lesions, depression, or substance use may lead to decreased food intake. New York State Department of Health AIDS Institute

Key Point Decreased food intake may be a direct result of disease processes, loss of structure in daily life, and/or how a patient feels about living with HIV infection. New York State Department of Health AIDS Institute

Malabsorption • Opportunistic or secondary infection, as well as neoplastic disease, of the bowel may lead to nutrient malabsorption. • Patients with diarrheal disease or painful lesions of the alimentary track may reduce food intake to avoid urgent or painful bowel movements. New York State Department of Health AIDS Institute

Key Point Diarrheal disease should be viewed as undernutrition with fluid and electrolyte loss. New York State Department of Health AIDS Institute

Altered Metabolism • Metabolic abnormalities may alter nutrient utilization, storage, or excretion from the body. • Abnormalities may be due to HIV infection itself or may be associated with specific antiretroviral medications.11-13 New York State Department of Health AIDS Institute

Metabolic abnormalities documented in association with HIV infection: • Elevated resting energy expenditure/basal metabolic rate • Increased dietary protein requirement • Decreased total and HDL cholesterol • Increased serum triglycerides and VLDL cholesterol • Low free testosterone (bioactive fraction) in association with wasting syndrome • Growth hormone resistance in association with wasting syndrome • Decreased visceral/abdominal and subcutaneous adipose tissue • Decreased bone mineral density New York State Department of Health AIDS Institute

Metabolic abnormalities associated with some antiretroviral medications: • Elevations in serum LDL cholesterol or triglycerides (some protease inhibitors) • Renal excretion of phosphorus and/or glucose (tenofovir) • Insulin resistance (protease inhibitor class effect) New York State Department of Health AIDS Institute

Sedentary Lifestyle Recommendation: Routinely counsel patients to engage in regularly scheduled resistance and aerobic exercise (AI).9,15 • Lack of routine scheduled resistance and aerobic exercise may lead to abdominal adiposity, sarcopenia, or diminished bone mineral density. • Weight gain in middle age is associated with excess risk of type 2 diabetes mellitus and cardiovascular disease events.16 New York State Department of Health AIDS Institute

Centers for Disease Control and Prevention exercise recommendations for adults are: • 150 minutes/week moderate intensity aerobic exercise and 2 sessions/week of resistance exercise working all major muscle groups or • 75 minutes/week vigorous aerobic exercise and 2 sessions /week resistance exercise or • Equivalent mix of moderate and vigorous aerobic exercise and 2 sessions/week resistance exercise New York State Department of Health AIDS Institute

Key Point Patients who are not obese or overweight should maintain a constant body weight throughout adulthood. New York State Department of Health AIDS Institute

Referral for Nutritional Services New York State Department of Health AIDS Institute

Recommendation:The following should prompt referral to a New York State certified nutritionist/registered dietitian for evaluation and patient-specific nutrition care plan (AIII)16: • Entry into HIV care • Unintentional weight loss >10% over 4 to 6 months • Chronic nausea, diarrhea, or vomiting • Severely dysfunctional psychosocial situation • Hyperglycemia • Dyslipidemia • New diagnosis of diabetes, hypertension, or renal disease • Two or more medical comorbidities • Annual or comprehensive visits • Abdominal adiposity New York State Department of Health AIDS Institute

Key Point Patients presenting with nutritional disorders may show involuntary weight loss, be over weight, and have increased dietary indiscretion. New York State Department of Health AIDS Institute

Comprehensive Nutrition Consultation New York State Department of Health AIDS Institute

Nutrition care consists of: • Assessment and intervention (including education in nutrition and the disease state) • Dietary counseling and self-management training • Pharmacological intervention • Food support or tube feeding or intravenous alimentation and routine follow up/reassessment New York State Department of Health AIDS Institute

Recommendation: nutrition consultation should include the following (AIII): • Patient complaints • Dietary evaluation • Demographics and clinical history • Clinical and anthropometric parameters • Functional tests as needed • Review of laboratory results • Review of medications focused on potential side effects • Social history including “supplement” use • Family history • Energy, protein, and micronutrient requirements • Intervention as needed with routine follow-up New York State Department of Health AIDS Institute

Investigation of Patient Complaints Recommendation: evaluate for (AIII): • Depression in patients complaining of “loss of appetite” or hyperphagia • Recent weight loss and period of time over which it occurred • Mistaken beliefs about nutrition, e.g., eating high fat foods will replace subcutaneous fat loss due to prior antiretroviral regimens with adipocyte /mitochondrial toxicity • Alimentary tract disease in those complaining of odynophagia or “diarrhea” • Access to cooking and refrigeration facilities • Ability to shop for ingredients and prepare meals New York State Department of Health AIDS Institute

Dietary Assessment Recommendation: Evaluation of dietary intake should include who prepares meals, where and with whom they are consumed, meal frequency, meal completion, quality and source of ingredients, cooking method and portion sizes. New York State Department of Health AIDS Institute

Nutritional Intake • Evaluate intake of concentrated protein (fish, poultry, meat, egg white), vegetables, whole grains and tubers, fruit, and sugar-sweetened beverages including juices or “juicing.” • Sugar-sweetened beverage intake should be discouraged due to linkage with diabetes, cardiovascular disease, diabetes and obesity.18 • Evaluate for patient use of processed/convenience foods especially prepared meats and canned goods due to their high sodium content. • Portion size models, e.g., 3 oz size or ½ cup size, are helpful in ascertaining usual portion size during the clinical encounter. • Use of fresh seasonal foods, locally grown when possible or frozen, and prepared at home should be strongly encouraged. New York State Department of Health AIDS Institute

Key Points • Food Stamp electronic benefits transfer (EBT) cards may be used at New York City farmers or “greenmarkets.” • Dietary sodium intake is largely from hidden sodium added during food processing, restaurant, fast food, and takeout meals. • Institute of Medicine (IOM) guidelines now recommend that most adults limit sodium intake to 1500 mg per day. New York State Department of Health AIDS Institute

Recommendations(AIII): • NYC clinics should post the locations of greenmarkets participating in the Food Stamp (EBT) program in waiting rooms (available at grownyc.org). • Adult patients should be referred to NYS certified nutritionist/registered dietitian for evaluation and education to achieve sodium intake reduction (to IOM recommendation). New York State Department of Health AIDS Institute

Demographics and Clinical History Recommendation: National Institutes for Health and World Health Organization assessment instruments should used to determine need for intervention and goals (AIII). New York State Department of Health AIDS Institute

Demographics and Clinical History • Nutritional interventions and their intensity should be based on assessment of potential benefit to the patient and the degree of disease event risk associated with the target abnormality. The patient’s willingness to execute dietary and other health behavior change is paramount. • National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII) should be used in evaluation. • WHO Fracture risk assessment tool (FRAX) should be used where clinically appropriate (men >50 y and postmenopausal women). • Clinical history should including duration of HIV infection, nadir CD4 count, history of opportunistic infection, wasting, and antiretroviral treatment history. New York State Department of Health AIDS Institute

Key Point: Osteoporosis Patients age and ethnicity (e.g., FRAX) may drive absolute osteoporosis risk. Historically, osteoporosis has been more prevalent in older Caucasian women and less so in African Americans. New York State Department of Health AIDS Institute

Clinical and Anthropometric Assessment Patients with HIV infection may present with wasting (involuntary loss of lean body mass and adipose tissue), sarcopenia (age-related loss of skeletal muscle with preservation or increase in adipose tissue), or lipodystrophy (focal or global loss of subcutaneous adipose tissue with preservation of visceral adipose tissue and skeletal muscle). New York State Department of Health AIDS Institute

Recommendation: evaluate for (AIII): • Body mass index (BMI), weight in kilograms/height in meters squared (NIH guidelines: undernutrition, <18.5; normal, 18.5 to 29.9; obese, >30) • % documented usual weight • Temporal wasting and facial lipoatrophy • Oral cavity for missing dentition, oral mucosal ulcers, (e.g., apthous or viral ulcers), malignancy (e.g., Kaposi’s sarcoma), fungal infections (e.g., oral candidiasis) • Neck circumference • Increase may associate with upper trunk adiposity and/or sleep apnea • Shoulders for angularity/prominent acromium process due to deltoid muscle loss • Trunk for increased clavicle prominence (subclavicular muscle loss) • Visible articulations of the ribs at the junction with the sternum consistent with subcutaneous fat loss New York State Department of Health AIDS Institute

Recommendation (continued): evaluate for (AIII): • Waist and hip circumferences • ATP III: abdominal obesity, male >40 inches, female >35 inches • Loss of hip circumference reflects gluteal-femoral subcutaneous fat loss and is associated with insulin resistance/type 2 diabetes mellitus. • Mid-upper arm circumference (non-dominant arm) • Less than 10th percentile NHANES may be consistent with wasting or lipodystrophy. Delayed skin-fold return is suggestive of dehydration. • Prominence of extremity vasculature consistent with subcutaneous fat loss • Mass of the interosseus dorsalis muscle by having the patient press the tip of his forefinger and thumb together • Muscle mass at the insertion of the quadriceps femoris and the vastus medialis with the patient’s leg positioned at a right angle. • Lower extremity edema (sacral edema bed rest patients). • In profoundly wasted patients; peri-orbital edema, ascities, and scrotal edema. New York State Department of Health AIDS Institute

Additional Anthropomorphic Tests • Bioelectrical impedance analysis (BIA) may be additive to physical examination. BIA indirectly measures tissue compartments, lean body mass (LBM), body cell mass (BCM), fat mass and extracellular (interstitial) mass (ECM). Phase-angle is a geometrical expression of the resistance and capacitance components of this assay. • Phase angle <5.6º and <4.8º are associated with diminished and non-survival, respectively.19 • ECM-to-BCM ratio of 1.3 or greater associated with non-survival.19 • Serial BIA over time describes weight loss or gain over time by soft tissue compartment quantifying response to clinical intervention. New York State Department of Health AIDS Institute

Key Point Patients with skeletal muscle loss may not always demonstrate weight loss if concurrent compartmental shift occurs, e.g., expansion adipose tissue or extracellular fluid depots. New York State Department of Health AIDS Institute

Functional Tests • There are concerns that long-term HIV infection may interfere with the normal aging process and accelerate it. Increased rates of cellular senescence may lead to loss of functional reserve over time. Several methods are available to evaluate for this. • Nutritional interventions such as protein, vitamin D, and calcium supplementation are first-line therapy for sarcopenia and osteopenia. Clinical investigators have documented decreased bone mineral density and increased non-traumatic fracture (fragility) risk in aging HIV-infected patients.20 Propensity to fall due to diminished hip, knee and ankle musculature often leads to fracture in older patients. Mid-life handgrip strength (Jamar Hand-grip dynamometer) and usual gait speed (timed walk) reflect total skeletal muscle and are predictive of future disability.21,22 New York State Department of Health AIDS Institute

Key Point Muscle function in addition to body mass should be evaluated in middle-aged and older patients. New York State Department of Health AIDS Institute

Laboratory Panels for Nutritional Aassessment Recommendation: Nutritional assessment should include evaluation of the following laboratory panels (AIII). • Complete metabolic panel • Lipid panel • Testosterone panel (men) • 25-[OH] vitamin D • Complete blood count New York State Department of Health AIDS Institute

Recommendation: Evaluate complete blood count for findings consistent with vitamin and/or mineral deficiency. Clinicians should be mindful of the bone marrow suppressive effect of HIV infection itself and elevated ferritin, an acute phase reactant, during opportunistic or secondary infection. New York State Department of Health AIDS Institute

Key Points • Patients with wasting and/or diarrheal disease may demonstrate profound hypophosphatemia, hypokalemia, and low magnesium. Hospitalized patients should receive intravenous replacement, as needed. • “Return to health effect” during the first two years of cART may manifest in elevation of total and LDL cholesterol in association with return to pre-illness diet. HDL cholesterol frequently remains low in spite of immune reconstitution with antiretroviral therapy.11 • HIV-infected men with wasting frequently demonstrate low free testosterone (hypogonadism). Repletion of skeletal muscle may be blunted in the absence of replacement therapy.23 • Low testosterone in older men in the general population has been linked to cardiovascular disease risk, sarcopenia, and insulin resistance. • Vitamin D deficiency is prevalent in HIV-infected patients in care.24 New York State Department of Health AIDS Institute

Medication and “Supplement” Review Recommendation: Nutrition consultation should include review of current medications, vitamins, and “supplements” (AIII). Herbal products and some vitamins at high dosage may interact with antiretroviral medications, enhance viral replication or contain undeclared prescription ingredients or other chemicals.25 Patients may disclose usage of what they consider to be dietary enhancements to their nutritionist/registered dietitian while neglecting to disclose them to their doctor during medication review. New York State Department of Health AIDS Institute

Key Point Herbal products are nonstandardized pharmaceuticals that may interact with antiretroviral medications and/or lead to toxicity. New York State Department of Health AIDS Institute

Social History Recommendation: evaluate for the following (AIII): • Tobacco use, alcohol use, other substance use • Scheduled routine resistance and aerobic exercise program New York State Department of Health AIDS Institute

Key Points • Patients should be counseled to engage in scheduled resistance exercise (in addition to aerobic) to achieve optimal peak bone density, maintain skeletal muscle and lessen fall risk later in life.26 • Education regarding diet and behavior, and bone mineral density should be provided to patients.26 New York State Department of Health AIDS Institute

Centers for Disease Control and Prevention exercise recommendations for adults are: • 150 minutes/week moderate intensity aerobic exercise and 2 sessions/week of resistance exercise working all major muscle groups or • 75 minutes/week vigorous aerobic exercise and 2 sessions /week resistance exercise or • Equivalent mix of moderate and vigorous aerobic exercise and 2 sessions/week resistance exercise New York State Department of Health AIDS Institute

Family History Recommendation: At least annually, update family history for cardiovascular disease, diabetes mellitus, end-stage kidney disease, and cancer(s) especially when occurring among first degree relatives (parents, siblings, offspring) (AIII). Evolving health history of a patient’s siblings may inform evaluation of seemingly minor clinical findings. New York State Department of Health AIDS Institute

Macronutrient Requirements: Caloric Requirement Recommendations: • Maintenance energy requirement (protein and non-protein calorie) should be calculated for persons who are hospitalized or in custodial care to insure provision of adequate nutrition (AIII). • Maintenance energy requirement should considered in determining planned caloric deficit for person’s participating in programs of caloric restriction to achieve weight loss (AIII). New York State Department of Health AIDS Institute

Caloric Requirement (continued) • Total energy expenditure (TEE) consists of: basal metabolic rate (BMR) or measured resting energy expenditure (REE) by indirect calorimetry (after a 12h fast, in a thermoneutral environment, upon awakening and prior to ambulation), dietary thermogenesis (DT), the thermic effect of food intake and energy expenditure of voluntary activity (EEA). To maintain weight stability (maintenance energy requirement) a patient’s caloric intake should equal TEE. • Weight Stability: TEE = REE + DT + EEA New York State Department of Health AIDS Institute

Nutrition and HIV/AIDS