title: Micronutrient supplementation for children with HIV infection.
abstract: BACKGROUND
  Micronutrient deficiencies are widespread and compound the effects of HIV disease in children, especially in poor communities. Micronutrient supplements may be effective and safe in reducing the burden of HIV disease. This review is an update of an earlier Cochrane review of micronutrient supplementation in children and adults which found that vitamin A and zinc are beneficial and safe in children exposed to HIV and living with HIV infection (Irlam 2010).
  
  
  OBJECTIVE
  To assess whether micronutrient supplements are effective and safe in reducing mortality and morbidity in children with HIV infection.
  
  
  METHODS
  The CENTRAL, EMBASE, and PubMed databases were searched for randomised controlled trials of micronutrient supplements (vitamins, trace elements, and combinations of these) using the search methods of the Cochrane HIV/AIDS Group.
  
  
  METHODS
  Randomised controlled trials were selected that compared the effects of micronutrient supplements with other supplements, or placebo or no treatment on the primary outcomes of mortality, morbidity, and HIV-related hospitalisations. Indicators of HIV disease progession, anthropometric measures, and any adverse effects of supplementation were secondary outcomes.
  
  
  METHODS
  Two reviewers independently screened and selected trials for inclusion, assessed the risk of bias using standardised criteria, and extracted data. Review Manager 5.1 was used to calculate the risk ratio (RR) for dichotomous data and the weighted mean difference (WMD) for continuous data, and to perform random effects meta-analysis where appropriate.
  
  
  RESULTS
  We included three new studies in addition to the eight studies in the earlier version of the review (Irlam 2010). Eleven studies with a total of 2412 participants were therefore included: five trials of vitamin A, one trial of vitamin D, two trials of zinc, and three trials of multiple micronutrient supplements. All except one trial were conducted in African children.Vitamin A halved all-cause mortality in a meta-analysis of three trials in African children, had inconsistent impacts on diarrhoeal and respiratory morbidity, and improved short-term growth in a Tanzanian trial. No significant adverse effects were reported.A single small trial of vitamin D in North American adolescents and children demonstrated safety but no clinical benefits. Zinc supplements reduced diarrhoeal morbidity and had no adverse effects on disease progression in one small South African trial. Another trial in South African children with and without HIV infection did not show benefit from the the prophylactic use of zinc or multiple supplements versus vitamin A in the small subgroup of children with HIV infection.Multiple micronutrient supplements at twice the RDA did not alter mortality, growth, or CD4 counts at 12 months in Ugandan children aged one to five years. Short-term supplementation until hospital discharge significantly reduced the duration of all hospital admissions in poorly nourished South African children, and supplementation for six months after discharge improved appetite and nutritional indicators.
  
  
  CONCLUSIONS
  Vitamin A supplementation is beneficial and safe in children with HIV infection. Zinc is safe and appears to have similar benefits on diarrhoeal morbidity in children with HIV as in children without HIV infection. Multiple micronutrient supplements have some clinical benefit in poorly nourished children with HIV infection.Further trials of single supplements (vitamin D, zinc, and selenium) are required to build the evidence base. The long-term effects and optimal composition and dosing of multiple micronutrient supplements require further investigation in children with diverse HIV disease status.
authors.affiliation: Primary Health Care Directorate, University of Cape Town, E47 OMB, Groote Schuur Hospital, Cape Town, Western Cape, South Africa, 7925.
authors.forename: James H
authors.initials: JH
authors.lastname: Irlam
authors.forename: Nandi
authors.initials: N
authors.lastname: Siegfried
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Visser
authors.forename: Nigel C
authors.initials: NC
authors.lastname: Rollins
mesh_terms: D000293:Adolescent; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000628:therapy; D015658:HIV Infections / Q000150:complications* / Q000401:mortality*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D018977:Micronutrients / Q000008:administration & dosage* / Q000172:deficiency; D016032:Randomized Controlled Trials as Topic; D014801:Vitamin A / Q000008:administration & dosage; D014807:Vitamin D / Q000008:administration & dosage; D014815:Vitamins / Q000008:administration & dosage; D015032:Zinc / Q000008:administration & dosage
chemical_list: D018977:Micronutrients; D014815:Vitamins; D014801:Vitamin A; D014807:Vitamin D; D015032:Zinc