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The purpose of this review was to assess whether micronutrient supplements are effective in reducing morbidity and mortality in adults and children with HIV infection.

Randomized controlled trials with the following criteria:

• Participants: Children and adults with confirmed HIV1 or HIV2 infection in a hospital, outpatient clinic or home-care setting
• Types of Intervention: Micronutrient supplements aimed at reducing the risk of mortality and morbidity in HIV-infected individuals, compared with placebo or no treatment. Micronutrients included vitamins (A, D, E, C, B₁, B₂, niacin, B₆, B₁₂, K, folate, beta-carotene), trace elements (zinc, selenium, magnesium, iodine, copper, manganese, chromium, cobalt, molybdenum), and combinations of the above only.
• Types of outcome measures: The primary outcomes considered were mortality and morbidity (HIV-associated and AIDS-defining infections, diarrhea, lower respiratory tract infections), hospital admissions and pregnancy outcomes. Secondary outcomes were viral load, markers of immune response (CD4, CD8 counts), serum levels of micronutrients, anthropometric measures, quality of life and adverse effects.

Trials of vitamin A supplementation of HIV-infected pregnant women were excluded.

Recruitment

The Cochrane Library (CENTRAL), EMBASE, MEDLINE, AIDSearch, CINAHL and conference proceedings were searched and pharmaceutical manufacturers and researchers in the field were contacted to locate any ongoing or unpublished trials.

Design

Systematic review. 

Three of the authors independently reviewed abstracts of the search results to determine which should be reviewed in full text. These were then independently assessed by all three for eligibility. Two authors independently appraised the eligible trials and extracted data using a standard data extraction form. The quality of each trial was appraised in terms of the method of randomization; whether allocation was concealed; blinding; losses to follow-up; and whether the analysis was by "Intent to Treat".

Statistical Analysis

Data on outcomes were entered into the Review Manager software. Relative risks were calculated for dichomotomous data and weighted mean differences for continuous data using a random effects model.

Timing of Measurements

Studies of varying lengths.

Dependent Variables

• Mortality and morbidity
• Hospital admissions
• Pregnancy outcomes
• Viral load
• Markers of immune response
• Serum levels of micronutrients
• Anthropometric measures
• Quality of life
• Adverse effects.  

Independent Variables

• Micronutrient supplementation compared with placebo or no treatment
• Micronutrients included vitamins, trace elements and combinations only.

 

 

Initial N

15 trials involving 3,643 participants met the inclusion criteria.

Attrition (Final N)

• 15 trials: Six trials were vitamin A and beta-carotene in adults; four were other micronutrients in adults; one trial was of multivitamins in pregnant and lactating women; and four trials were vitamin A in children.
• 21 trials were excluded due to inadequate randomization of participants, use of interventions that were not exclusively micronutrients or because the outcomes were not relevant to the review.

Location

Worldwide studies. 

 

Other Findings

• Six trials comparing vitamin A and beta-carotene with placebo in adults failed to show any effects on mortality, morbidity, CD4 and CD8 counts or on viral load
• Four trials of other micronutrients in adults did not affect overall mortality, although there was a reduction in mortality in a low CD4 subgroup
• In a large Tanzanian trial in pregnant and lactating women, daily multivitamin supplementation was associated with a number of benefits to both mothers and children: A reduction in maternal morbidity from AIDS-related causes; a reduced risk of progression to stage IV disease; fewer adverse pregnancy outcomes; less diarrheal morbidity; and a reduction in early-child mortality among immunologic- and nutritional-compromised women
• Vitamin A alone reduced all-cause mortality and improved growth in a small sub-group of HIV-infected children in one hospital-based trial, and reduced diarrhea-associated morbidity in a small HIV-infected sub-group of infants in another trial.

There is no conclusive evidence at present to show that micronutrient supplementation effectively reduces morbidity and mortality among HIV-infected adults. It is reasonable to support the current WHO recommendations to promote and support adequate dietary intake of micronutrients at RDA levels whenever possible. There is evidence of benefit of vitamin A supplementation in children. The long-term clinical benefits, adverse effects, and optimal formulation of micronutrient supplements require further investigation.

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