Upload
joan-hunt
View
215
Download
1
Tags:
Embed Size (px)
Citation preview
What Food and Micronutrients Should
Be Provided for HIV-infected Patients
Wafaie FawziDepartments of Nutrition and Epidemiology
Harvard School of Public Health
Reduction in production in a household with an AIDS death, Zimbabwe
Source: Stover & Bollinger, 1999
•
•
•
•
•
Crops Reduction in output
Maize
Cotton
Vegetables
Groundnuts
Cattle owned
49%
37%
29%
47%
61%
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 ?
• 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•Iron and Folic Acid•Vitamin A•Vitamins B-complex, C and E•Zinc•Selenium
MATERNAL VITAMIN A LEVELS AND MOTHER-TO-CHILD TRANSMISSION OF HIV-1
Semba, Lancet 1994;343:1593
Ve
rtic
al t
ran
sm
iss
ion
of
HIV
-1 %
Serum Vitamin A (µmol/L)
REGIMEN
1. VITAMIN A ALONE (n=270)
2. MULTIVITAMINS EXCLUDING VIT A (n=269)
3. MULTIVITAMINS INCLUDING VIT A (n=266)
4. PLACEBO (n=264)
• PREFORMED VIT A : 5000 IU
• β-CAROTENE : 30 mg
• 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
1. & 3. VITAMIN A 200,000 IU
2. & 4. PLACEBO
DA
ILY
@ DELIV
ER
Y
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
PATIENT CARE
EFFECT OF MULTIVITAMIN EFFECT OF MULTIVITAMIN SUPPLEMENTATION ON FETAL DEATHSSUPPLEMENTATION ON FETAL DEATHS
OutcomeMultivitamins
n (%)
No Multivitamin
sn (%)
RR (95%CI) P
Miscarriage
12 (2.3) 18 (3.5)0.66 (0.32-
1.36)0.26
Stillbirth 18 (3.5) 31 (6.1)0.58 (0.33-
10.2)0.05
Fetal death 30 (5.9) 49 (9.6)0.61 (0.39-
0.94)0.02
Fawzi, Lancet 1998;351:1477
EFFECT OF VITAMIN A SUPPLEMENTATION EFFECT OF VITAMIN A SUPPLEMENTATION ON FETAL DEATHSON FETAL DEATHS
OutcomeVitamin A
n (%)No Vitamin A
n (%)RR (95%CI) P
Miscarriage
13 (2.5) 17 (3.4)0.73 (0.36-
1.50)0.39
Stillbirth 25 (4.8) 24 (4.8)1.00 (0.58-
1.73)1.00
Fetal death 38 (7.3) 41 (8.2)0.89 (0.58-
1.36)0.59
Fawzi, Lancet 1998;351:1477
EFFECT OF MULTIVITAMIN EFFECT OF MULTIVITAMIN SUPPLEMENTATION ON PREGNANCY SUPPLEMENTATION ON PREGNANCY
OUTCOMESOUTCOMES
OutcomeMultivitamin
sn (%)
No Multivitamins
n (%)RR (95%CI) P
LBW (<2500g) 36 (8.8) 62 (15.8) 0.56 (0.38-0.82) 0.003
LBW (<2000g) 7 (1.7) 16 (4.1) 0.42 (0.18-1.01) 0.05
Preterm (<37wk)
96 (21.1) 106 (24.5) 0.86 (0.68-1.10) 0.23
Preterm (<34wk)
28 (6.2) 44 (10.2) 0.61 (0.38-0.96) 0.03
SGA 39 (10.0) 66 (17.6) 0.57 (0.39-0.82) 0.002
Fawzi, Lancet 1998;351:1477
EFFECT OF VITAMIN A SUPPLEMENTATION EFFECT OF VITAMIN A SUPPLEMENTATION ON PREGNANCY OUTCOMESON PREGNANCY OUTCOMES
OutcomeVitamin A
n (%)No Vitamin A
n (%)RR (95%CI) P
LBW (<2500g) 47 (11.6) 51 (13.0) 0.89 (0.61-1.29) 0.54
LBW (<2000g) 11 (2.7) 12 (3.1) 0.89 (0.40-1.98) 0.77
Preterm (<37wk)
105 (23.4) 97 (22.1) 1.06 (0.83-1.35) 0.66
Preterm (<34wk)
38 (8.5) 34 (7.7) 1.09 (0.70-1.70) 0.70
SGA 48 (12.4) 57 (15.0) 0.83 (0.58-1.18) 0.29
Fawzi, Lancet 1998;351:1477
EFFECT OF VITAMIN A SUPPLEMENTATION EFFECT OF VITAMIN A SUPPLEMENTATION ON HIV INFECTION OF OFFSPRINGON HIV INFECTION OF OFFSPRING
Fawzi, AIDS 2002;16:1935
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.
MULTIVITAMINS DECREASED THE RISK OF MULTIVITAMINS DECREASED THE RISK OF INFECTION THROUGH BREASTFEEDING IN INFECTION THROUGH BREASTFEEDING IN
POPULATION SUBGROUPSPOPULATION SUBGROUPS
↓ L
YM
PH
0.99
0.37
1.01
0.48
1.03
0.51
1.07
0.27
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8↑
LYM
PH
HB ≥
85 g
/LH
B <
85 g
/L
ESR <
81 m
m/h
ESR ≥
81 m
m/h
BW
≥ 2
500 g
BW
< 2
500 g
RELATIVE RISK
P=0.03 P=0.06 P=0.06P=0.04
Fawzi, AIDS 2002;16:1935
MULTIVITAMINS DECREASED THE RISK OFMULTIVITAMINS DECREASED THE RISK OFDEATH BY 24 MONTHS IN POPULATION DEATH BY 24 MONTHS IN POPULATION
SUBGROUPSSUBGROUPS
Fawzi, AIDS 2002;16:1935
↓ L
YM
PH
↑ LY
MPH
VIT
E ≥
9.6
μm
ol/L
RELATIVE RISK
0.96
0.30
1.31
0.31
0.0
0.5
1.0
1.5
2.0
2.5
3.0
VIT
E <
9.6
μm
ol/L
P=0.05 P=0.008
MULTIVITAMINS DECREASED THE RISK OFMULTIVITAMINS DECREASED THE RISK OFHIV INFECTION OR DEATH BY 24 MONTHS HIV INFECTION OR DEATH BY 24 MONTHS
IN POPULATION SUBGROUPSIN POPULATION SUBGROUPS
Fawzi, AIDS 2002;16:1935
↓ L
YM
PH
↑ LY
MPH
RELATIVE RISK
P=0.06 P=0.01
0.96
0.50
0.98
0.36
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
ESR <
81 m
m/h
ESR ≥
81 m
m/h
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 GroupDifference = 151 cells/L (95% CI, 64-237 cells/ L ; P=.0006
CID 2003:36;1053-62
Effect of Maternal Vitamin Effect of Maternal Vitamin Supplements Supplements
on Child Anemiaon 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 Effect of Maternal Vitamin Supplements Supplements
on Child Growthon 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 scoresby 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 Effect of Maternal Vitamin Supplements Supplements
on Child Developmenton 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 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
•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)• 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
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)
Effect of Three Vitamin Regimens on Viral Load Compared to the
Placebo GroupViral Load (log 10)
Difference P_________________________________________________________________________________________________
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. 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
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
• 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
Stage 4 or AIDS-Related Death
No. of Events
Relative Risk (95% CI)*
P
Whole Period
Multivitamins B, C and E 67 0.71 (0.51, 0.98) 0.04
Multivitamins and Vitamin A 70 0.80 (0.58, 1.10) 0.17
Vitamin A alone 79 0.88 (0.64 1.19) 0.40
Placebo Group 83 1.0
Fawzi et al., NEJM 2004
Kaplan-Meier Curves of Progression to WHO Stage 4 or Death, by Regimen
0.6
0.7
0.8
0.9
1.0
0 12 24 36 48 60 72
Months after randomization
Fra
ctio
n a
live
wit
h st
age
< 4
Multivitamins B, C, and EMultivitamins and Vitamin AVitamin A alonePlacebo
No. at risk Multivitamins B, C, and E 271 195 157 119 Multivitamins and Vitamin A
267 181 143 102
Vitamin A alone 272 190 147 104 Placebo 267 173 145 101
Fawzi et al., NEJM, 2004
Multivitamins and HIV-Related Complications Multivitamins and HIV-Related Complications
Fawzi et al., NEJM, 2004
Effect of Multivitamins on Postpartum Wasting
RR MVITS vs. PLACEBO = 0.66 (0.47, 0.94)
Villamor et al., AJCN, 2005.
0.50
0.55
0.60
0.65
0.70
0.75
0.80
0.85
0.90
0.95
1.00
0 2 4 6 8 10 12 14 16 18 20 22 24
TIME (mo)
P (
MU
AC
≥ 2
2 cm
)
PLACEBO
VITAMIN A
MULTIVITAMINS
MVITS + VIT A
Effects of Multivitamins on Hemoglobin Concentrations (g/dL)
PeriodPlacebo(N=219)Mean (SD)
MVits(N = 228)Difference
PMVits + A(N = 226)Difference
PVit A Alone(N=233)Difference
P
Whole Period
10.84 (1.31)
0.20 (0.00,0.40)
0.05 0.21 (0.02, 0.40)
0.03 0.04 (-0.16,0.23)
0.70
Up to 70 Days Postpartum
10.16 (1.87)
0.59 (0.22, 0.97)
0.002
0.53 (0.15, 0.91)
0.006 0.32 (-0.06,0.70)
0.10
First 2 Years
10.64 (1.49)
0.37 (0.13, 0.62)
0.003
0.36 (0.12, 0.60)
0.003 0.17 (-0.08,0.42
0.18
First 4 Years
10.88 (1.42)
0.27 (0.06, 0.48)
0.01 0.27 (0.07, 0.48)
0.009 0.09 (-0.12,0.30)
0.42
Fawzi et al., 2006
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
• 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 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
• 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
–AnthropometryBMI, Weight, Height/Length
–Dietary AssessmentDietary Recall, Food Frequency
Questionnaires
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 - 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
• 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
• 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 < 21Third trimester : BMI <
22
Future Directions : Implementation
and Public Health EvaluationMicronutrient 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 EvaluationMacronutrients/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 ?