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, B(1), B(2), niacin, B(6), B(12), C, D and E, folate, zinc, copper, iodine and selenium); or the standard recommended dietary allowance of six multivitamins (vitamins A, D(2, )B(1), B(2), 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00122941