Iron supplementation in HIV-infected Malawian children with anemia: a double-blind, randomized, controlled trial.

BACKGROUND: It is unknown whether iron supplementation in human immunodeficiency virus (HIV)-infected children living in regions with high infection pressure is safe or beneficial. A 2-arm, double-blind, randomized, controlled trial was conducted to examine the effects of iron supplementation on hemoglobin, HIV disease progression, and morbidity. METHODS: HIV-infected Malawian children aged 6-59 months with moderate anemia (hemoglobin level, 7.0-9.9 g/dL) were randomly assigned to receive 3 mg/kg/day of elemental iron and multivitamins (vitamins A, C, and D) or multivitamins alone for 3 months. Participants were followed for 6 months. RESULTS: A total of 209 children were randomly assigned to treatment, and 196 (93.8%) completed 6 months of follow-up. Iron supplementation was associated with greater increases in hemoglobin concentrations (adjusted mean difference [aMD], 0.60; 95% confidence interval [CI], .06-1.13; P = .03) and reduced the risk of anemia persisting for up to 6 months follow-up (adjusted prevalence ratio, 0.59; 95% CI, .38-.92; P = .02). Children who received iron had a better CD4 percentage response at 3 months (aMD, 6.00; 95% CI, 1.84-10.16; P = .005) but an increased incidence of malaria at 6 months (incidence rate, 120.2 vs 71.7; adjusted incidence rate ratio [aIRR], 1.81 [95% CI, 1.04-3.16]; P = .04), especially during the first 3 months (incidence rate, 78.1 vs 36.0; aIRR, 2.68 [95% CI, 1.08-6.63]; P = .03). CONCLUSIONS: Iron supplementation in anemic HIV-infected children has beneficial effects on hemoglobin, anemia, and immunity but increases the risk of malaria. Thus, iron supplementation in HIV-infected children living in malaria-endemic areas should only be provided in combination with adequate protection from malaria. CLINICAL TRIALS REGISTRATION: ISRCTN-62947977.

Iron deficiency in children with HIV-associated anaemia: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to determine the prevalence of iron deficiency in HIV-infected children from high- and low-income settings and compared it with that of HIV-uninfected controls. We searched five major databases for primary studies reporting on anaemia and iron markers in HIV-infected children. A pooled analysis was done using random-effects models, with Forest plots and heterogeneity test estimates provided. Fifteen articles (2778 children) met the inclusion criteria. In the pooled analysis, mean overall prevalence of iron deficiency in HIV-infected children was 34% (95%CI 19-50%). Prevalence rates were similar in high-income (31%; 95%CI 2-61%) and low-income settings (36%; 95%CI 17-54%) (p=0.14). Studies that included a HIV-uninfected control population (n=4) were only available from low-income settings and showed less iron deficiency in HIV-infected children (28%) than in HIV-uninfected children (43%); OR 0.50 (0.27-0.94); p=0.03. The findings suggest that HIV-infected children are less likely to be iron deficient when compared with HIV-uninfected children. Possible explanations for this include HIV-induced haematosuppression and associated hypoferraemia, with adequate iron stores. Nevertheless iron deficiency is a common co-morbidity in HIV. Studies are needed to determine the role of iron deficiency in HIV-associated anaemia and the effects of iron supplementation in this population.