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What Food and Micronutrients Should Be Provided for HIV-infected Patients

What Food and Micronutrients Should Be Provided for HIV-infected Patients. Wafaie Fawzi Departments of Nutrition and Epidemiology Harvard School of Public Health. HIV. Nutrition. exacerbates. Interaction of HIV and Nutrition. impairs. Maize. 61%. Cotton. 47%. Vegetables. 49%.

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What Food and Micronutrients Should Be Provided for HIV-infected Patients

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  1. What Food and Micronutrients Should Be Provided for HIV-infected Patients Wafaie FawziDepartments of Nutrition and EpidemiologyHarvard School of Public Health

  2. HIV Nutrition exacerbates Interaction of HIV and Nutrition impairs

  3. Maize 61% Cotton 47% Vegetables 49% Groundnuts 37% Cattle owned 29% Reduction in production in a household with an AIDS death, Zimbabwe Crops Reduction in output • • • • • Source: Stover & Bollinger, 1999

  4. Why Food and Micronutrients? Immune-stimulation - Lower viral load – Slower disease progression Strengthen epithelial integrity - Lower transmission Reduce inflammation - Role in wasting Maternal supplementation may lead to a more robust immune and GI system in the newborn - additional defense Mehta S and Fawzi W. Vitam Horm 2007;75:355-83

  5. Overview – Are Micronutrient Supplements Beneficial in HIV Infection ? • Perinatal and Child Outcomes • Mother-to-Child Transmission • Child Morbidity and Mortality • Adult Outcomes: - Immunological and Virological Progression - Clinical Disease Progression and Mortality

  6. Micronutrients and Pregnancy Outcomes among HIV-positive women • Iron and Folic Acid • Vitamin A • Vitamins B-complex, C and E • Zinc • Selenium

  7. Vertical transmission of HIV-1 % Serum Vitamin A (µmol/L) MATERNAL VITAMIN A LEVELS AND MOTHER-TO-CHILD TRANSMISSION OF HIV-1 Semba, Lancet 1994;343:1593

  8. B1 : 20 mg • B2 : 20 mg • B6 : 25 mg • NIACIN: 100 mg • B12 : 50 µg • C : 500 mg • E : 30 mg • FOLATE: 0.8 mg REGIMEN • PREFORMED VIT A : 5000 IU • β-CAROTENE : 30 mg 1. VITAMIN A ALONE (n=270) 2. MULTIVITAMINS EXCLUDING VIT A (n=269) DAILY 3. MULTIVITAMINS INCLUDING VIT A (n=266) 4. PLACEBO (n=264) 1. & 3. VITAMIN A 200,000 IU @ DELIVERY 2. & 4. PLACEBO

  9. PATIENT CARE All women received the following during pregnancy: • Daily ferrous sulphate (400 mg equivalent to 120 mg ferrous iron) • Daily folate (5 mg) • Weekly chloroquine phosphate (500 mg ≈ 300 mg base) • Standard prenatal care services including: • Regular visits, clinical assessment, laboratory investigation, and appropriate treatment • Continued psychosocial assessment, counseling and support

  10. EFFECT OF MULTIVITAMIN SUPPLEMENTATION ON FETAL DEATHS Fawzi, Lancet 1998;351:1477

  11. EFFECT OF VITAMIN A SUPPLEMENTATION ON FETAL DEATHS Fawzi, Lancet 1998;351:1477

  12. EFFECT OF MULTIVITAMIN SUPPLEMENTATION ON PREGNANCY OUTCOMES Fawzi, Lancet 1998;351:1477

  13. EFFECT OF VITAMIN A SUPPLEMENTATION ON PREGNANCY OUTCOMES Fawzi, Lancet 1998;351:1477

  14. EFFECT OF VITAMIN A SUPPLEMENTATION ON HIV INFECTION OF OFFSPRING Fawzi, AIDS 2002;16:1935

  15. Vitamin A Trial among HIV-infected Women Zimbabwe • Examined efficacy of a single large dose of vitamin A given to women in the early postpartum period (400,000 IU) and/or to neonates (50,000 IU). • Supplementing mothers or infants resulted in increased risk of HIV-infection or death, although providing the supplement to both mother and infant was apparently not different from placebo. • Among the majority of infants, namely those who were PCR negative at 6 weeks, all three vitamin A regimens were significantly associated with an ~2-fold higher mortality. Humphrey et al.

  16. MULTIVITAMINS DECREASED THE RISK OF INFECTION THROUGH BREASTFEEDING IN POPULATION SUBGROUPS RELATIVE RISK 1.8 P=0.04 P=0.06 P=0.06 P=0.03 1.6 1.4 1.2 1.07 1.03 0.99 1.01 1.0 0.8 0.6 0.51 0.48 0.4 0.37 0.27 0.2 0.0 ↑LYMPH ↓ LYMPH HB ≥85 g/L HB <85 g/L ESR <81 mm/h ESR ≥81 mm/h BW ≥ 2500 g BW < 2500 g Fawzi, AIDS 2002;16:1935

  17. MULTIVITAMINS DECREASED THE RISK OF DEATH BY 24 MONTHS IN POPULATION SUBGROUPS 3.0 2.5 2.0 1.5 1.31 1.0 0.96 0.5 0.31 0.30 0.0 RELATIVE RISK P=0.05 P=0.008 ↑LYMPH ↓ LYMPH VIT E ≥9.6 μmol/L VIT E <9.6 μmol/L Fawzi, AIDS 2002;16:1935

  18. MULTIVITAMINS DECREASED THE RISK OF HIV INFECTION OR DEATH BY 24 MONTHS IN POPULATION SUBGROUPS RELATIVE RISK P=0.06 P=0.01 1.6 1.4 1.2 1.0 0.98 0.96 0.8 0.6 0.50 0.4 0.36 0.2 0.0 ↑LYMPH ↓ LYMPH ESR <81 mm/h ESR ≥81 mm/h Fawzi, AIDS 2002;16:1935

  19. CD4 cell counts among children of HIV Infected Mothers Who Were Not Known to be HIV Infected at 6 weeks of age, According to Maternal Multivitamin Group Difference = 151 cells/L (95% CI, 64-237 cells/ L ; P=.0006 CID 2003:36;1053-62

  20. Effect of Maternal Vitamin Supplements on Child Anemia • Compared with placebo, multivitamins including B-complex, C and E, reduced risk of: • Anemia (HB <8.5) by 27% (95% CI: 5-43) • Severe hypochromic microcytosis by 49% (95% CI: 16-69) • Macrocytosis by 63% (95% CI: 21-72) • Vitamin A alone had no effect on all outcomes Fawzi et al, 2006

  21. Effect of Maternal Vitamin Supplements on Child Growth • Multivitamins (B-complex, C,E): • Increased attained weight by 459 g (95% CI: 35-882); P=0.03 • Increased weight-for age z scores by 0.42 (95% CI: 0.07-0.77); P=0.02 • Increased weight-for-length z scores by 0.38 (95% CI: 0.07-0.68); P=0.01 • Vitamin A alone had no effect on child growth Villamor et al., AJCN, 2005.

  22. Effect of Maternal Vitamin Supplements on Child Development • Multivitamins (B-complex, C and E): - Increased Psychomotor Development Index score by 2.6 (95% CI: 0.1-5.1) • Reduced the risk for developmental delay on the motor scale by 60% (95% CI: 30-80) • Had no effect on mental development • Vitamin A alone had no effect on mental or motor development McGrath et al., Pediatrics, 2006.

  23. Overview – Are Micronutrient Supplements Beneficial in HIV Infection ? • Perinatal and Child Outcomes • Mother-to-Child Transmission • Child Morbidity and Mortality • Adult Outcomes: - Immunological and Virological Progression - Clinical Disease Progression and Mortality

  24. Micronutrients and HIV Disease Progression • Vitamin A • Vitamins B-complex, C and E • Zinc • Selenium • Iron

  25. B Vitamins in Multiples of RDA and HIV-1 Mortality (Tang et al. 1996) • Vitamin B1 (>=5 x RDA) • RR=0.61, 95% CI: 0.38-0.98 • Vitamin B2 (>=5 x RDA) • RR=0.60, 95% CI: 0.37-0.97 • Vitamin B6 (>=2 x RDA) • RR=0.60, 95% CI: 0.39-0.93

  26. Supplemental B Vitamins and Progression to AIDS and Death in South African HIV-infected Patients(Kanter et al. 1999) • Observational study • Black patients in Jo-Burg 1985-1997 • Median time to progression=32.0 weeks for those without vitamins versus 72.7 for those who took vitamins (P=0.0044) • Median survival for patients without vitamins=144.8 weeks and 264.4 weeks for those who took B vitamins (P=0.0014)

  27. Effect of Three Vitamin Regimens on Viral Load Compared to the Placebo Group Viral Load (log 10) Difference P _________________________________________________________________________________________________

  28. Vitamin E and C Supplementation and Viral Load in HIV-infected persons (Allard et al. 1998) • Randomized placebo-controlled, double blinded trial. • N=49 • Duration=3 mo • 800 IU daily of alpha-tocopherol and 1000 mg daily of vitamin C Or daily placebo

  29. Vitamin E and C Supplementation and Viral Load in HIV-infected persons (Allard et al. 1998) • Significant increase in plasma vitamins E and C levels • Significant reduction in lipid peroxidation markers • Trend towards reduction in viral load: -Mean -0.45 log (SD=0.39) versus +0.50 log (SD=0.40) P=0.10

  30. Randomized Trial of Multiple Micronutrients and Mortality among Thai HIV-positive patients (Jiamton et al, 2003) • Randomized placebo-controlled • N=481, duration=48 weeks • Overall death: RR=0.53, P=0.10 • Among those with CD4 <200: RR=0.37, P=0.05 • Among those with CD4 <100: RR=0.26, P=0.03

  31. Trial of Vitamins, Tanzania • Factorial design of Vitamin A, and Multivitamins B-complex, C, and E • Women enrolled during pregnancy • Followed up for median of 6 years • Monthly assessments of clinical signs • Regular assessment of CD4+ count, HB concentration, and viral load • High compliance Fawzi et al., NEJM, 2004

  32. Effect of Multivitamins on HIV Disease Progression Stage 4 or AIDS-Related Death Fawzi et al., NEJM 2004

  33. Kaplan-Meier Curves of Progression to WHO Stage 4 or Death, by Regimen Fawzi et al., NEJM, 2004

  34. Multivitamins and HIV-Related Complications Fawzi et al., NEJM, 2004

  35. 1.00 0.95 0.90 0.85 0.80 MULTIVITAMINS P (MUAC ≥ 22 cm) 0.75 MVITS + VIT A VITAMIN A 0.70 PLACEBO 0.65 0.60 0.55 0.50 0 2 4 6 8 10 12 14 16 18 20 22 24 TIME (mo) Effect of Multivitamins on Postpartum Wasting RR MVITS vs. PLACEBO = 0.66 (0.47, 0.94) Villamor et al., AJCN, 2005.

  36. Effects of Multivitamins on Hemoglobin Concentrations (g/dL) Fawzi et al., 2006

  37. Wasting and Growth Failure Wasting or involuntary weight loss is a hallmark of HIV disease Decreased dietary intake is a major contributor Poor Appetite Malabsorption Increased energy expenditure Co-morbidities

  38. Nutrition-based Interventions Zambia Provision of monthly household food ration (comprising of micronutrient-fortified corn-soya blend from World Food Programme) to food insecure patients starting ART significantly increased CD4 counts at 12 months among the recipients compared to the non-recipients The food supplements also led to a significant increase in adherence to ART by approximately 40% among the recipients as compared to the non-recipients. Both these results remained significant after adjusting for sex, WHO stage, and BMI at entry However, there was no significant difference in weight gain in the two groups Megazzini K, et al. Abstract MOAB0401 XVI International AIDS Conference 2006

  39. Overview – Are Micronutrient Supplements Beneficial in HIV Infection ? • Perinatal and Child Outcomes • Mother-to-Child Transmission • Child Morbidity and Mortality • Adult Outcomes: - Immunological and Virological Progression - Clinical Disease Progression and Mortality

  40. Recommendations: Public Health Practice Nutritional Assessment A comprehensive nutritional assessment at baseline and during follow-up will help target nutrition support for malnourished patients; such nutrition support is likely to help maximize the benefits of antiretroviral treatment particularly on HIV disease progression Anthropometry BMI, Weight, Height/Length Dietary Assessment Dietary Recall, Food Frequency Questionnaires

  41. Recommendations - Micronutrients For HIV-infected pregnant women - a MV (B, C, E) is likely to help - this intervention has already been applied in various settings MV is possibly beneficial for HIV-infected persons in pre-ART stages to slow disease progression May enhance compliance, preserve ART for later stages, avert A/Es and decrease resistance associated with ART, result in improving QOL as well as Rx related cost

  42. Recommendations - Micronutrients Vitamin A supplementation of HIV-infected pregnant women is to be avoided Periodic vitamin A supplementation of children after six months of age No conclusive evidence for other minerals or elements Concerns about universal iron supplementation in pregnant women

  43. Recommendations - Macronutrients Increase total energy intake Asymptomatic - ~10% Symptomatic - ~20-30% Children - 50-100% Energy and nutrient-dense foods needed to fulfill this need Ready to use supplementary and therapeutic foods (RUSF, RUTF) Plumpy Nut (an energy-dense, fortified peanut butter/milk powder-based paste) Fortified foods Fortified, blended flours (e.g. corn-soya blend (CSB))

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