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

Wafaie FawziDepartments of Nutrition and EpidemiologyHarvard School of Public Health

interaction of hiv and nutrition

HIV

Nutrition

exacerbates

Interaction of HIV and Nutrition

impairs

reduction in production in a household with an aids death zimbabwe

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

why food and micronutrients
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

overview are micronutrient supplements beneficial in hiv infection
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

micronutrients and pregnancy outcomes among hiv positive women
Micronutrients and Pregnancy Outcomes among HIV-positive women
  • Iron and Folic Acid
  • Vitamin A
  • Vitamins B-complex, C and E
  • Zinc
  • Selenium
slide9

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

regimen

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

patient care
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
vitamin a trial among hiv infected women zimbabwe
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.

slide20

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

slide21

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

slide22

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

slide23

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

effect of maternal vitamin supplements on child anemia
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

effect of maternal vitamin supplements on child growth
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.

effect of maternal vitamin supplements on child development
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.

overview are micronutrient supplements beneficial in hiv infection1
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

micronutrients and hiv disease progression
Micronutrients and HIV Disease Progression
  • Vitamin A
  • Vitamins B-complex, C and E
  • Zinc
  • Selenium
  • Iron
b vitamins in multiples of rda and hiv 1 mortality tang et al 1996
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
slide31
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)
slide32

Effect of Three Vitamin Regimens on Viral Load Compared to the Placebo Group

Viral Load (log 10)

Difference P

_________________________________________________________________________________________________

vitamin e and c supplementation and viral load in hiv infected persons allard et al 1998
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

vitamin e and c supplementation and viral load in hiv infected persons allard et al 19981
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

slide35
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

trial of vitamins tanzania
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

effect of multivitamins on hiv disease progression
Effect of Multivitamins on HIV Disease Progression

Stage 4 or AIDS-Related Death

Fawzi et al., NEJM 2004

slide40

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.

wasting and growth failure
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

nutrition based interventions
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

overview are micronutrient supplements beneficial in hiv infection2
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

recommendations public health practice
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

recommendations micronutrients
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

recommendations micronutrients1
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

recommendations macronutrients
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))

recommendations management of malnutrition
Recommendations – Management of Malnutrition
  • Definitions/Entry criteria for Severe Malnutrition
    • Children: Weight for height Z-score < -2
    • Adults: BMI < 17 kg/m2
    • Pregnant women: First trimester: BMI < 20 Second trimester BMI < 21 Third trimester : BMI < 22
future directions implementation and public health evaluation
Future Directions : Implementation and Public Health Evaluation

Micronutrient Supplementation:

Effectiveness of Single vs. Multiple RDA

Direct multivitamin supplementation of children

MV supplementation and HAART

Micronutrients and HIV/TB co-infection

Safety and efficacy of minerals: Fe, Se

future directions implementation and public health evaluation1
Future Directions : Implementation and Public Health Evaluation

Macronutrients/Food:

Are food supplements necessary ? Do you they affect drug adherence ? Do they have clinical benefits ?

Is food insecurity an issue that affects all individuals, regardless of HIV status ?

Who should receive food supplements ? What entry criteria ? What Exit criteria ?

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