Effect of multiple micronutrient supplementation on survival of HIV-infected children in Uganda: a randomized, controlled trial.
BACKGROUND
Micronutrient deficiencies compromise the survival of HIV-infected children in low-income countries. We assessed the effect of multiple micronutrient supplementation on the mortality of HIV-infected children in Uganda.


METHODS
In a randomized, controlled trial, 847 children aged one to five years and attending HIV clinics in Uganda were stratified by antiretroviral therapy (ART, n = 85 versus no ART, n = 762). The children were randomized to six months of either: twice the recommended dietary allowance of 14 micronutrients as the intervention arm (vitamins A, B1, B2, niacin, B6, B12, C, D and E, folate, zinc, copper, iodine and selenium); or the standard recommended dietary allowance of six multivitamins (vitamins A, D2, B1, B2, C and niacin) as a comparative "standard-of-care" arm. Mortality was analyzed at 12 months of follow up using Kaplan Meier curves and the log rank test.


RESULTS
Mortality at 12 months was 25 out of 426 (5.9%) children in the intervention arm and 28 out of 421 (6.7%) in the comparative arms: risk ratio 0.9 (95% CI 0.5 - 1.5). Two out of 85 (2.4%) children in the ART stratum died compared with 51 out of 762 (6.7%) in the non-ART stratum. Of those who died in the non-ART stratum, 25 of 383 (6.5%) were in the intervention arm and 26 of 379 (6.9%) in the comparative arm; risk ratio 1.0 (95% CI 0.6 - 1.6). There was no significant difference in survival at 12 months (p = 0.64, log rank test). In addition, there was no significant difference in mean weight-for-height at 12 months; 0.70 +/- 1.43 (95% CI 0.52 - 0.88) for the intervention versus 0.59 +/- 1.15 (95% CI 0.45 - 0.75) in the comparative arm. The mean CD4 cell count; 1024 +/- 592 (95% CI 942 - 1107) versus 1060 +/- 553 (95% CI 985 - 1136) was also similar between the two groups.


CONCLUSIONS
Twice the recommended dietary allowance of 14 micronutrients compared with a standard recommended dietary allowance of six multivitamins for six months was well tolerated, but it did not significantly alter mortality, growth or CD4 counts. Future intervention studies should carefully consider: (1) the composition and dosing of the supplements; and (2) the power needed to detect a difference between arms.


BACKGROUND
ClinicalTrials.gov Identifier: NCT00122941.
Ndeezi
Grace
G
Department of Paediatrics and Child Health, Makerere University, Kampala, Uganda. gracendeezi@yahoo.com
Tylleskär
Thorkild
T
Ndugwa
Christopher M
CM
Tumwine
James K
JK
D018791:CD4 Lymphocyte Count; D002675:Child, Preschool; D019587:Dietary Supplements / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality*; D006801:Humans; D007223:Infant; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage*; D013534:Survival; D014454:Uganda; D014815:Vitamins / Q000008:administration & dosage
D018977:Micronutrients; D014815:Vitamins