Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2013 Oct 11;2013(10):CD010666.
doi: 10.1002/14651858.CD010666.

Micronutrient supplementation for children with HIV infection

James H Irlam  1 , Nandi Siegfried, Marianne E Visser, Nigel C Rollins
Affiliations
Meta-Analysis

Micronutrient supplementation for children with HIV infection

James H Irlam et al. Cochrane Database Syst Rev. .

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).

Objectives: To assess whether micronutrient supplements are effective and safe in reducing mortality and morbidity in children with HIV infection.

Search 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.

Selection criteria: 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.

Data collection and analysis: 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.

Main 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.

Authors' 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.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

1
1
Results of search of PubMed, EMBASE, and CENTRAL from Jan. 2010 to July 2011 (RCTs in child populations only)
2
2
Risk of bias summary: review of authors' judgements about risk of bias in each included study
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Meta‐analysis of mortality in Vitamin A trials
1.1
1.1. Analysis
Comparison 1 Vitamin A, Outcome 1 All‐cause mortality.
1.2
1.2. Analysis
Comparison 1 Vitamin A, Outcome 2 Child growth at 12 months.
2.1
2.1. Analysis
Comparison 2 Vitamin D, Outcome 1 CD4 counts at 12 months.
2.2
2.2. Analysis
Comparison 2 Vitamin D, Outcome 2 Viral load at 12 months.
3.1
3.1. Analysis
Comparison 3 Zinc, Outcome 1 Viral load at 9 months.
3.2
3.2. Analysis
Comparison 3 Zinc, Outcome 2 Mortality at 9 months.
3.3
3.3. Analysis
Comparison 3 Zinc, Outcome 3 CD4 % at 9 months.
3.4
3.4. Analysis
Comparison 3 Zinc, Outcome 4 Clinic visits.
4.1
4.1. Analysis
Comparison 4 Multiple micronutrients, Outcome 1 Mortality at 12 months.
4.2
4.2. Analysis
Comparison 4 Multiple micronutrients, Outcome 2 CD4 count.
4.3
4.3. Analysis
Comparison 4 Multiple micronutrients, Outcome 3 Duration of hospitalisation.
4.4
4.4. Analysis
Comparison 4 Multiple micronutrients, Outcome 4 Change in appetite at 6 months.
4.5
4.5. Analysis
Comparison 4 Multiple micronutrients, Outcome 5 Anthropometric Z scores.
See this image and copyright information in PMC

References

References to studies included in this review

Arpadi 2009 {published data only}
    1. Arpadi SM, McMahon D, Abrams EJ, Bamji M, Purswani M, Engelson ESetal. Effect of bimonthly supplementation with oral cholecalciferol on serum 25‐hydroxyvitamin D concentrations in HIV‐infected children and adolescents. Pediatrics 2009;123(1):e121‐6. - PMC - PubMed
Bobat 2005 {published data only}
    1. Bobat, R, Coovadia, H, Stephen, C, et al. Safety and efficacy of zinc supplementation for children with HIV‐1 infection in South Africa: A randomised double‐blind placebo‐controlled trial. Lancet 2005;366(9500):1862‐7. - PubMed
Coutsoudis 1995 {published data only}
    1. Coutsoudis A, Bobat RA, Coovadia HM, Kuhn L, Tsai WY, Stein ZA. The effects of vitamin A supplementation on the morbidity of children born to HIV‐infected women. American Journal of Public Health 1995;85(8):1076‐81. - PMC - PubMed
Fawzi 1999 {published data only}
    1. Fawzi WW, Mbise R, Hertzmark E, Fataki MR, Herrera MG, Ndossi G, et al. A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus‐infected and uninfected children in Tanzania. The Pediatric Infectious Disease Journal 1999;18(2):127‐33. - PubMed
    1. Fawzi WW, Mbise R, Spiegelman D, Fataki M, Hertzmark E, Ndossi G. Vitamin A supplements and diarrheal and respiratory tract infections among children in Dar es Salaam, Tanzania. The Journal of Pediatrics 2000;137(5):660‐7. - PubMed
    1. Villamor E, Mbise R, Spiegelman D, Hertzmark E, Fataki M, Peterson KE, et al. Vitamin A supplements ameliorate the adverse effect of HIV‐1, malaria, and diarrheal infections on child growth. Pediatrics 2002;109(1 (E6)):1‐10. - PubMed
Hanekom 2000 {published data only}
    1. Hanekom WA, Yogev R, Heald LM, Edwards KM, Hussey GD, Chadwick EG. Effect of vitamin A therapy on serologic responses and viral load changes after influenza vaccination in children infected with the human immunodeficiency virus. The Journal of Pediatrics 2000;36(4):550‐2. - PubMed
Hussey 1996 {published data only}
    1. Hussey G, Hughes J, Potgieter S, Kessow G, Burgess J, Beatty Detal. Vitamin A status and supplementation and its effect on immunity in children with AIDS. XVII International Vitamin A Consultative Group (IVACG) Meeting, Guatemala City. 1996:81.
Luabeya 2007 {published data only}
    1. Chhagan MK, Broeck J, Luabeya KK, Mpontshane N, Tomkins A, Bennish ML. Effect on longitudinal growth and anemia of zinc or multiple micronutrients added to vitamin A: a randomized controlled trial in children aged 6‐24 months. BMC public health 2010;10:145. [PUBMED: 20298571] - PMC - PubMed
    1. Chhagan MK, Broeck J, Lubaeya KK, Mpontshane N, Tucker KL, Bennish ML. Effect of micronutrient supplementation on diarrhoeal disease among stunted children in rural South Africa. European journal of clinical nutrition 2009;63(7):850‐7. - PMC - PubMed
    1. Luabeya, K. K, Mpontshane, N, Mackay, M, et al. Zinc or multiple micronutrient supplementation to reduce diarrhea and respiratory disease in South African children: A randomized controlled trial. PLoS ONE 2007;2(6):e541. - PMC - PubMed
Mda 2010a {published data only}
    1. Mda S, Raaij JM, Villiers FP, MacIntyre UE, Kok FJ. Short‐term micronutrient supplementation reduces the duration of pneumonia and diarrheal episodes in HIV‐infected children. The Journal of nutrition 2010;140(5):969‐74. [PUBMED: 20335632] - PubMed
Mda 2010b {published data only}
    1. Mda S, Raaij JM, Macintyre UE, Villiers FP, Kok FJ. Improved appetite after multi‐micronutrient supplementation for six months in HIV‐infected South African children. Appetite 2010;54(1):150‐5. [PUBMED: 19815042] - PubMed
Ndeezi 2010 {published data only}
    1. Ndeezi G, Tylleskar T, Ndugwa CM, Tumwine JK. Effect of multiple micronutrient supplementation on survival of HIV‐infected children in Uganda: a randomized, controlled trial. Journal of the International AIDS Society 2010;13:18. [PUBMED: 20525230] - PMC - PubMed
Semba 2005 {published data only}
    1. Semba RD, Ndugwa C, Perry RT, Clark TD, Jackson JB, Melikian Getal. Effect of periodic vitamin A supplementation on mortality and morbidity of human immunodeficiency virus‐infected children in Uganda: A controlled clinical trial. Nutrition 2005;21(1):25‐31. - PubMed

References to studies excluded from this review

Chatterjee 2010 {published data only}
    1. Chatterjee A, Bosch RJ, Hunter DJ, Manji K, Msamanga GI, Fawzi WW. Vitamin A and vitamin B‐12 concentrations in relation to mortality and morbidity among children born to HIV‐infected women. Journal of tropical pediatrics 2010;56(1):27‐35. [PUBMED: 19502599] - PMC - PubMed
CIGNIS 2010 {published data only}
    1. Chilenje Infant Growth, Nutrition and Infection (CIGNIS) Study Team. Micronutrient fortification to improve growth and health of maternally HIV‐unexposed and exposed Zambian infants: a randomised controlled trial. PloS one 2010;5(6):e11165. [PUBMED: 20567511] - PMC - PubMed
    1. Filteau S, Baisley K, Chisenga M, Kasonka L, Gibson RS. Provision of micronutrient‐fortified food from 6 months of age does not permit HIV‐exposed uninfected Zambian children to catch up in growth to HIV‐unexposed children: a randomized controlled trial. Journal of acquired immune deficiency syndromes (1999) 2011;56(2):166‐75. [PUBMED: 21119523] - PubMed

Additional references

Aggarwal 2007
    1. Aggarwal R, Sentz J, Miller MA. Role of zinc administration in prevention of childhood diarrhea and respiratory illnesses: a meta‐analysis. Pediatrics 2007;119(6):1120‐30. [PUBMED: 17545379] - PubMed
ASSaf 2007
    1. Irlam J, Hussey G, Dhansay M. The effects of nutritional interventions in HIV/AIDS: Micronutrients. In: Assaf Study Panel, editor(s). HIV/AIDS, TB and Nutrition: Scientific inquiry into the nutritional influences on human immunity with special reference to HIV infection and active TB in South Africa. Pretoria: Academy of Science of South Africa, 2007:143‐51.
Baeten 1993
    1. Beaton G, Martorell R, Aronson KJ, Edmonston B, McCabe G, Ross AC, Harvey B. Effectiveness of vitamin A supplementation in the control of young child morbidity and mortality in developing countries. ACC/SCN State of the Art Series, Nutrition Policy Paper No 13 1993.
Baqui 2002
    1. Baqui AH, Black RE, Arifeen S, Yunus M, Chakraborty J, Ahmed S, et al. Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. British Medical Journal 2002;325(7372):1059. - PMC - PubMed
Bhandari 2002
    1. Bhandari N, Bahl R, Taneja S, Strand T, Molbak K, Ulvik RJ, et al. Substantial reduction in severe diarrheal morbidity by daily zinc supplementation in young north Indian children. Pediatrics June 2002;109(6):e86. - PubMed
Bhutta 1999
    1. Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A, et al. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group. The Journal of pediatrics 1999;135(6):689‐97. [PUBMED: 10586170] - PubMed
Bhutta 2000
    1. Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, et al. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. The American journal of clinical nutrition 2000;72(6):1516‐22. [PUBMED: 11101480] - PubMed
Black 2010
    1. Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet 2010;375(9730):1969‐87. [PUBMED: 20466419] - PubMed
Filteau 2001
    1. Filteau SM, Rollins NC, Coutsoudis A, Sullivan KR, Willumsen JF, Tomkins AM. The effect of antenatal vitamin A and beta‐carotene supplementation on gut integrity of infants of HIV‐infected South African women. Journal of pediatric gastroenterology and nutrition 2001;32(4):464‐70. [PUBMED: 11396815] - PubMed
GradePro 2008 [Computer program]
    1. Jan Bozek, Andrew Oxman, Olger Schunemann. Gradepro. Version 3.2.2 for Windows. GRADE Working Group, 2008.
Haider 2008
    1. Haider B, Bhutta Z. Review of vitamin A supplementation in the neonatal period. Web appendix to Bhutta et al, 2008. Available at: http://www.globalnutritionseries.org/web_appendices (accessed on 24.09.2008) 2008.
Horton 2008
    1. Horton S, Begin F, Greig A, Lakshman A. Copenhagen Consensus best practices paper on Micronutrient supplements for child survival (Vitamin A and Zinc). Copenhagen Consensus Center Working Paper 2008.
Micronutrient Initiative 2009
    1. The Micronutrient Initiative. Investing in the Future: A United Call to Action on Vitamin and Mineral Deficiencies. http://www.unitedcalltoaction.org/flashreport.asp (accesssed 8 June 2010) 2009.
Piwoz 2000
    1. Piwoz EG, Preble EA. HIV/AIDS and Nutrition: A Review of the Literature and recommendations for Nutritional Care and Support in sub‐Saharan Africa. Refugee Studies Centre. Washington: Support for Analysis and Research in Africa (SARA) Project, Academy for Educational Development, 2000.
Robberstad 2004
    1. Robberstad B, Strand T, Black RE, Sommerfelt H. Cost‐effectiveness of zinc as adjunct therapy foracute childhood diarrhea in developing countries. WHO Bulletin 2004;82(7):523‐31. - PMC - PubMed
Strand 2002
    1. Strand TA, Chandyo RK, Bahl R, Sharma PR, Adhikari RK, Bhandari N, et al. Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young children. Pediatrics 2002;109(5):898‐903. - PubMed
UNAIDS 2010
    1. UNAIDS. UNAIDS Report on the Global AIDS Epidemic 2010. http://www.unaids.org/globalreport/ Accessed 14 Novemeber 2011.
UNICEF 2007
    1. UNICEF. Vitamin A Supplementation ‐ A decade of progress. UNICEF report 2007.
UNICEF 2009
    1. UNICEF. Tracking Progress on Child and Maternal Nutrition: A survival and development priority. New York: UNICEF Division of Communication, November 2009. [ISBN 978‐92‐806‐4482‐1]
Wagstaff 2004
    1. Wagstaff A, Cleason M. The Millennium Development Goals for health: rising to the challenges. Washington DC: World Bank 2004.
WHO 2003
    1. World Health Organisation. WHO Technical Consultation on Nutrient Requirements for People Living with HIV/AIDS. Nutrient Requirements for People Living with HIV/AIDS. Geneva: World Health Organisation, 2003.
WHO 2009
    1. World Health Organization. Handbook IMCI Integrated Management of Childhood Illness for High HIV Settings. Geneva: World Health Organization, 2009. - PubMed
WHO/UNICEF 2004
    1. WHO/UNICEF. Clinical Management of Acute Diarrhea. WHO/UNICEF Joint Statement 2004.
Zinc Investigators Collaborative Group 2000
    1. Zinc Investigators Collaborative Group. Therapeutic effects of oral zinc in acute and persistent diarrhoea in children in developing countries: Pooled analysis of randomized controlled trials. Am J Clin Nutr 2000;72:1516‐22. - PubMed

References to other published versions of this review

Irlam 2010
    1. Irlam J, Visser ME, Rollins NC, Siegfried N. Micronutrient supplementation in children and adults with HIV infection. Cochrane Database of Systematic Reviews 2010, Issue 12. [DOI: 10.1002/14651858.CD003650.pub3] - DOI - PubMed

Publication types

LinkOut - more resources