Manifestations of HIV Infection Primary InfectionClinical LatencyAdvanced Disease often asymptomatic or overlooked symptoms 1-6 weeks after infection viral like syndrome: sore throat, fever, lymphadenopathy, rash differential includes EBV, CMV, hepatitis, toxoplasmosis antibody (ELISA, Western Blot) may not be detected usually asymptomatic lymph nodes site of ongoing viral latency massive viral production destruction of CD4 cells a decrease in lean body mass without apparent total body weight change vitamin B12 deficiency increased susceptibility to food and water-borne pathogens. Symptomatic Plasma viremia begins to rise CD4 cell count falls further A decline in nutrient status or body composition Opportunistic infections develop: fever, weight loss, lymphadenopathy, thrush, diarrhea, malignancies, wasting syndrome, neurologic syndrome including dementia
Medication Side Effects and how they relate to eating, food --------- MALNUTRITION Anorexia Sore/dry/painful mouth Swallowing difficulties Constipation/Diarrhea Nausea/Vomiting/Altered Taste Depression/Tiredness/Lethargy
Malnutrition can... √ Contribute to impaired immune response √ Result in more rapid disease progression & shortened survival √ Contribute to increased frequency and severity of infections √ Result in fatigue, loss of appetite, sense of taste and smell, and decreased quality of life √ Decrease tolerance to therapy and lessen medication efficacy
Weight Loss: Independent Predictor of Mortality Weight loss and wasting have been predominant features of HIV disease progression since the beginning of the HIV/AIDS epidemic and have long been established as strong predictors of morbidity and mortality in patients infected with HIV.
Weight Loss: Independent Predictor of Mortality With the advent of HAART and prophylaxis for opportunistic infections, many AIDS-defining illnesses that were previously frequent are now rarely seen in successfully treated patients.
Weight Loss: Independent Predictor of Mortality So the prevalence of HIV-related wasting syndrome has greatly diminished ; however, several studies have concluded that patients treated with HAART were still at risk for wasting. Wanke et al. found that ~1/3 of HIV-infected patients in the NFHL study who were treated with HAART were still at risk for wasting. Thus weight loss, regardless of treatment status, remains a strong predictor of death.
Pathophysiology AIDS Wasting Oxidative StressMicronutrient Deficiency Malabsorption/ Dysphagia Dietary Intake Negative Energy Balance Intestinal Parasites Protein Loss Fat Loss HIV Opportunistic Infection Immune Function Pro-inflammatory Cytokines (TNF alpha) Anorexia Metabolic Rate Endocrine Disorder Skeletal Protein Breakdown J AIDS 1988
Potential Mechanisms of AIDS Wasting 1) Increased energy expenditure 2) Decreased energy intake 3) Altered metabolism 4) Hormonal Alterations
AIDS-related Wasting Syndrome Profound involuntary weight loss > 10% of baseline BW accompanied by fever or weakness and chronic diarrhea for >30 days Weight loss or wasting even with adequate or increased calorie intake Decrease in LBM without weight loss during pre-symptom phase
Wasting is diagnosed …. Lose 7.5% over 6 months OR 10% over 12 months BMI drops below 20
Nutritional Problems (cont) Diarrhea and malabsorption can result from direct HIV infection in the intestine but are more often caused by other pathogens such as bacteria, Crytosporidium, or herpes simplex that take advantage of the depressed immune system. Medications can interfere with eating by causing GI discomfort, nausea, vomiting, diarrhea, and altered taste Depression often leads to isolation, apathy, neglect of self-care, and diminished appetite – all which can affect immunocompetence Socioeconomic factors play an important role in whether the patient can afford adequate and nutritious food.
Altered Metabolism Early studies documented weight loss and protein depletion in untreated patients The application of HAART has led to a decreased incidence of malnutrition Syndrome of altered body fat distribution has emerged (lipodystrophy) associated with PIs Hypertriglyceridemia, hypercholesterolemia, and insulin resistance are commonly seen in patients treated with HAART therapy.
Nutritional Problems Decreased appetite may result from fever, pain, fatigue, emotional stress, and altered sensations of taste and smell due to medication side effects. Lactose intolerance is an early effect of HIV on the intestinal tract due to the loss of lactase. The HIV infection changes the structure of the gut wall, resulting in a decreased lactase level. Intolerance results in fermentation causing abdominal cramping and a bloated feeling. Oral Lesions, caused by Candida albicans, herpes, or Kaposi’s sarcoma can make chewing and swallowing difficult and painful.
What Causes Lipodystrophy? Syndrome most likely has a multi-factorial etiology Most patients who have lipodystrophy started noticing symptoms while they were on triple-drug therapy. Lipodystrophy was first reported among patients taking combinations of drugs that included a protease inhibitor (PI). There are also some patients who have experienced one or more symptoms of lipodystrophy without taking any anti-HIV drugs at all. It's still not clear what role these anti-HIV drugs play in the development of lipodystrophy.
Nutrition Assessment Screen for Nutrition Concerns at initial visit and each visit there after including: Assess HIV infection-related symptoms experiencing Assess dietary patterns, food availability, nutrient intake, erratic and/or inadequate intakes Assess use of non-traditional therapies Assess psychosocial conditions, income, and insurance Assess anthropometric measurements Assess lab values
WHO Screening nurse may assess nutritional status, but need tools to ask right questions Physicians may assess nutritional status – generally physicians refer to: DIETITIAN - Ryan White Services pay for Nutrition Counseling for HIV patients. Others are charged, based on income, as assessed, using a sliding fee scale discussed during the appointment.
Nutrition Assessment - Physical Height, Weight, BMI Use accurate techniques Check routinely – record and monitor change Body composition BMI Fat distribution changes Shape changes RED FLAGS – wt change since last time and/or BMI <20 Ask questions about why weight changes, look for clinical signs of deficiencies/excesses
Lab Values related to nutrients Albumin Iron Lipid Profile Renal Function Tests Blood Sugar
Complimentary and Alternative Therapies St Johns Wart decreases blood levels of indinivir – may cause drug resistance and treatment failure Garlic supplements have been shown to reduce blood level of saquinavir Milk thistle (silymarin) could lessen metabolism of medication and increase toxicity High use of any Complimentary/Alternative Therapy is costly and may lead to toxicity or interfere with medications
Diet Therapy INDIVIDUALIZE! Help maintain your health and quality of life by having your nutrition reassessed every 3-6 months.
Nutrition Care Process Prioritize most urgent issues Intervention goals Prevent adverse events to therapies Restore adequate nutritional status Do Diet Prescription
Nutrition is important for - health - immune system. NEED: high-quality foods for energy & strength
High-quality foods from all the food groups Grains: choose whole grains for fiber Whole grain breads and cereal, whole wheat pasta, oatmeal, brown rice, couscous, barley, quinoa, whole wheat tortillas Hepatitis C: plan a diet high in carbohydrates to help spare your protein Fats & Oils: Choose heart healthy fats Olive oil, canola oil Fat offers twice as many calories as protein and carbohydrates
High-quality foods from all the food groups Fruits & Vegetables: VARIETY is important Aim for as many colors and types of fruits and vegetables possible Choose 100% juice for immune system support
High-quality foods from all the food groups Dairy Products: calcium is important Low-fat/non-fat milk, cheese, yogurt, soy products
High-quality foods from all the food groups Meat & Protein: bake, roast, or grill— Don’t fry Chicken, turkey, fish rich in omega-3’s (salmon, sardines, mackerel), eggs, nuts, seeds, tofu, lentils, beans HIV/AIDS: increase protein to fight fever & infections Hepatitis C: keep protein at individual recommended levels to spare your liver
High-quality foods from all the food groups Fats & Oils: Choose heart healthy fats Olive oil, canola oil Fat offers twice as many calories as protein and carbohydrates
Diet Therapy: Fat Varies in tolerance bases on individual Assess fat for malabsorption – diarrhea MCT to reduce steatorhea, abdominal cramps Omega-3 fatty acids may improve immune function Follow usual guidelines for elevated cholesterol & triglyceride Include soluble fiber, plant sterols, soy protein, and cholesterol saturated factors
DIET THERAPY: Calories 500 calories above Energy Expenditure at Rest (EER) = 40-50 calories/kg Example 180 pound man – 82 kgs = 3600 calories/day
Diet Therapy: Protein 1.0 g/kg to 1.4 g/kg for maintenance 1.5 g/kg to 2.0 g/kg for replacing Only restrict is severe liver or kidney disease with doctors order
Diet Therapy: FLUIDS & ELECTROLYTES Fluid = 30 to 35 ml/kg During times of diarrhea extra fluid (2 cups/day) and electrolytes for night sweats, diarrhea, and fever Pedialyte, kool-ade with salt, jello, broth
Diet Therapy: Vitamins and Minerals Actual status is seldom identifiable in labs Gather patient self-reported intake Suggest 100% One-A-Day with minerals (calcium, Iron, Magnesium) Suggest Basic Vitamin B-Supplement Go for higher doses if diarrhea is prolonged, anemia develops or dietary deficiencies are evident
Nutrition Counseling Medicaid – 4 sessions/year Medicare – 4 sessions/year Public Health – sliding scale Diet order from physician Receive an assessment Receive a Diet Prescription – not just nutrition but food Carbs will be added after Protein, fat and glucose tolerance is considered
Macronutrients VS. Micronutrients MACRO Carbohydrate Protein Fat Water MICRO Vitamins Minerals Antioxidants
High Quality, High Calorie Snack Ideas: Carnation Instant Breakfast, 1 packet (130 calories, 6 g protein) Cheese & crackers, 3 cheese slices + 5 butter crackers (425 calories, 22 g protein) Eggnog, 1 cup (350 calories, 10 g protein) Ensure, Homemade Van.(8 oz) (250 calories, 9 g protein) Boost, Vanilla (8 oz) (240 calories, 10 g protein) Whole grain cereal/ whole milk (350 calories, 15 g protein) Cheese pizza + medium soda (420 calories, 12 g protein) Mixed Nuts, 2 oz (350 calories, 20 g protein) Kraft® Macaroni & Cheese, 3/4 C. (250 calories, 10 g protein)
High Calories Snack Ideas: Glazed donut, 2 (360 calories, 6 g protein) Dairy Queen® blizzard, small (520 calories, 10 g protein) · McDonalds® McFlurry, 12 oz (600 calories, 15 g protein) Snickers®, king-size (540 calories, 9 g protein)
Diet Prescription Increase calories Increase protein Increase fiber Increased fruit and veggies Food safety Drug-nutrient interactions Perhaps anti-diarrheal, pancreatic or lactase enzymes
Nutritional Supplements in HIV Infection to counteract AIDS Wasting MVI Glutamine Carnitine Appetite Stimulant Insulin Sensitizing Agents Anti-catabolic medications Resistance Training
Role of Micronutrients in the Pathogenesis of HIV infection Micronutrients play important roles in maintaining immune function and SLOW reactive oxidant destruction Micronutrient deficiencies are common among HIV infected persons – nature of disease and malnutrition Micronutrient deficiency has been associated with further immunopression, oxidative stress, speeds up HIV replication and CD4+ T-cell depletion. (semba)
Vitamin E and C Conclusion: Supplements of vitamin E &C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies Aids - 10 September 1998 - Volume 12 - Issue 13 - p 1653-1659
Glutamine Application in HIV/AIDS Glutamine is the most abundant amino acid in the body and is considered a conditionally essential amino acid during periods of catabolism. During periods of increased metabolic stress, glutamine is released freely from the skeletal muscle, and intracellular glutamine concentrations fall by more than 50% Increased synthesis of glutamine in the skeletal muscle often results in muscle-wasting syndrome Glutamine synthesis cannot keep up with the higher requirements during stress. – ADD - high-protein foods including beef, chicken, fish, beans, and dairy products. Individuals deficient in glutamine manifest changes in gut morphology including increased membrane permeability resulting in bacterial translocation, malabsorption, and diarrhea
Glutamine Application in HIV/AIDS (cont…) Data suggest that glutamine supplementation offers the potential to limit skeletal muscle wasting, reduce diarrhea and malabsorption, enhance immune host defense, and reduce the incidence of opportunistic infections associated with HIV infection and AIDS Shabert J et al. Med Hypotheses. 1996;46:252-256
L-Carnitine in HIV Infection Carnitine is a conditionally essential amino acid found predominantly in red meat. It is also found in milk (human and cow’s), pork, lamb, tempeh, and supplements. It is conditionally essential because the body can make it from lysine and methionine with assistance from Vitamin C and other compounds produced in the body. Carnitine is synthesized in the Kidney and stored in the muscles. Carnitine’s function is to shuttle long-chain fatty acids into the mitochondria to be utilized as fuel. HIV/AIDS is a risk factor for carnitine deficiency
Appetite Stimulant: Dronabinol Derived from delta-9-tetrahydrocannabinol (major active component of Marijuana) Useful in decreasing nausea and increasing appetite Insignificant gains or even loss of total BW May induce central nervous system events such as anxiety, confusion, emotional lability and hallucinations, possibly addictive. Treatment Guidelines for HIV Associated Wasting, Mayo Clinic Proceedings, April 2000
Appetite Stimulant: Megestrol Acetate (Megace) A synthetic derivative of the natural steroid hormone, progesterone. Improved appetite in a number of studies Takes two weeks for effect. Considerable increases in BW, although mostly in body fat May be due to testosterone lowering effect, not reversed by supplementation w/testosterone May induce or exacerbate DM, cause adrenal insufficiency when abruptly discontinued after long-term use Treatment Guidelines for HIV Associated Wasting, Mayo Clinic Proceedings, April 2000
Appetite Stimulants Sips of wine (Mogan David) Chocolate Culantro – long leafed different than cilantro
Resistance Training Supervised exercise training is a promising anabolic strategy for pts with AIDS. Studies of exercise training have shown increased muscle function, wt gain, strength, LBM. Effects of resistance training alone in AIDS wasting pts remains unknown. However, use of resistance training with growth hormone replacement has been shown to be effective in AIDS pts with AIDS wasting. Journal of the American Medical Association, April 14 199, Volume 281(14), pp 1282-1290. The New England Journal of Medicine, June 3 1999
Summary HIV/AIDS remains an epidemic worldwide Malnutrition is a complication in HIV related morbidity and mortality Weight loss is an independent predictor of mortality Despite HAART, patients remain at risk for AIDS wasting syndrome Contributors of AIDS wasting syndrome include increased energy expenditure, decreased energy intake, altered metabolism, and hormonal factors Good food from variety of whole grains, beans and animal protein, More Matters for fruit and veggies, calcium – VITAL! Multivitamin supplementation could reduce the risk of or delay HIV-associated disease and mortality. Data suggest glutamine supplementation may help limit skeletal muscle wasting
Summary (cont) Pts have been found to be deficient in Carnitine, may benefit from supplementation since it may have antiapoptic effect through antioxidant activity. Appetite Stimulants may result in wt gain, but mostly in adding fat and may also have some negative side effects. Testosterone deficiency may lead to wasting, supplementation may be beneficial leading to improved sense of well being, strength, etc, however Testosterone over use may damage liver. Correction of Growth Hormone resistance may help reverse wasting, but it is a costly intervention if pt does not have Medicaid. Short term use has been shown to be beneficial. Resistance training has been shown to increase wt and LBM, but one study found that training plus growth hormone was most beneficial.
References Semba RD, Tang AM. Micronutrients and the pathogenesis of human immunodeficiency virus infection. Br J Nutrition 1999;81:181-9. Fawzi WW, Msamanga GI, Spiegelman D, et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Medicine 2004;351:23-32. Melchior JC, Niyongabo T, Henzel D, et al. Malnutrition and wasting, immunodepression, and chronic inflammation as independent predictors of survival in HIV-infected patients. Nutrition 1999; 15:865-9 Suttmann U, Ockenga J, Selberg O, et al. Incidence and prognostic value of malnutrition and wasting in human immunodeficiency virus-infected outpatients. J Acquir Immune Defic Syndrome Hum Retrovirol 1995;8:239-46. Silva M. Skolnik PR, Gorbach Sl, et al. The effect of protease inhibitors on weight and body composition n HIV-infected patients. AIDS 1998; 12:1645-51. Wanke CA, Silva M, Knox TA, et al. Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy. Clin Infect Dis 2000; 31:803-5 Tang, Alice M. et al. Weight loss and survival in HIV-Positive Patients in the Era of Highly Active Antiretroviral Therapy. JAIDS 2002;31:230-236 Mittendorfer B, Gore D, Herndon D, et al. Accelerated glutamine synthesis in critically ill patients cannot maintain normal intramuscular free glutamine concentration. J Parenter Enteral Nutri. 1999;23:243-252.
References Kotler, Donald P. Nutritional Alterations Associated with HIV infection. JAIDS 2000;25:81-87 Ott M, Lambke B, Fischer H, et al. Early changes of body composition in human immunodeficiency virus-infected patients: tetrapolar body impedance analysis indicates significant malnutrition. Am J Clin Nutr 1993;57:15-19 Melchior JC, Salmon D, Rigaud D, et al. Resting energy expenditure is increased in stable, malnourished HIV-infected patients. AM J Clin Nutr 1991;53:437-41 Rivera S, Briggs W, Qian D, et al. HIV RNA levels correlate with prior weight loss. Mulligan k, Tai VW, Schambelan M. Energy expenditure in human immunodeficiency virus infection. N engl J Med 1997; 336:70-1. HIV Prevalence in the United States, 2000. 9th Conference on Retroviruses and Opportunistic Infections, Seattle, Wash., Feb. 24-28, 2002. Abstract 11. Centers for Disease Control and Prevention (CDC). HIV and AIDS - United States, 1981-2001. MMWR 2001;50:430-434.4 Centers for Disease Control and Prevention (CDC). HIV Prevention Strategic Plan Through 2005. January 2001.5. Centers for Disease Control and Prevention (CDC). HIV/AIDS Surveillance Report 2002;14:1-40. Gerrior, Jul. Nutritional Challenges in HIV Infection. Tufts University School of Medicine Nutrition Infection Unit
References Morretti, et al. Effect of L-Carnitine on Human Immunodeficiency Virus-1 Infection-Associated Apoptosis: A Pilot Study, Blood, Vol 91, No. 10, May 15, 1998: pp 3817-3824 Treatment Guidelines for HIV Associated Wasting, Mayo Clinic Proceedings, April 2000, Volume 75(4), pp 386-394. Drug Therapy: Treatments for Wasting in Patients with the Acquired Immunodefeciency Syndrome, The New England Journal of Medicine, June 3 1999, Volume 340(22), pp 1740-50. Strawford, et al. Resistance Exercise and Supraphisilogic Androgen Thearpy in Eugonadal Men with HIV-Related Weight Loss: A Randomized Controlled Trial, Journal of the American Medical Association, April 14 1999, Volume 281(14), pp 1282-1290. Shabert J, Winslow C, Lacey JM. Wilmore DW. Glutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Nutrition 1999;15:860-864. Shabert JK, Wilmore DW. Glutamine deficiency as a cause of human immunodeficiency virus wasting. Med Hypotheses 1996;46:252-256.