BACKGROUNDIron-related genes and iron status may independently contribute to variable HIV outcomes. The nature of the biologically plausible gene-nutrient interaction remains unknown.OBJECTIVESThe objectives were to investigate whether iron-related genotypes and clinically abnormal iron status independently predict mortality in HIV and whether a gene-nutrient interaction exists.DESIGNBaseline plasma, DNA, and clinical data were obtained from 1362 HIV-seropositive Gambian adults followed for 11.5 y to ascertain all-cause mortality. Iron status was estimated on the basis of plasma iron, soluble transferrin receptor (sTfR), ferritin, transferrin, transferrin index, and log(sTfR/ferritin). One haptoglobin (HP) and 5 SLC11A1 (NRAMP1) polymorphisms were genotyped.RESULTSSLC11A1-SLC3 and CAAA polymorphisms were the best independent genetic predictors of mortality [adjusted mortality rate ratio (95% CI)]: SLC3:G/C = 0.59 (95% CI: 0.45, 0.85), CAAA:del/ins = 1.51 (95% CI: 1.10, 2.07). In an adjusted model that included all polymorphisms, SLC1:199/199, SLC1:other/other, SLC6a:A/A, and CAAA:del/ins were associated with significantly greater mortality, whereas Hp 2-1 and SLC3:G/C were protective. In unadjusted analyses, all biomarker concentrations were significantly associated with mortality. In an extension of previous findings, both low and elevated iron states were associated with mortality, but the nature of the risk was variable, with linear, inversely linear, and U-shaped associations depending on the biomarker. Mortality was significantly lower in HIV-2 than in HIV-1 infection in the presence of abnormal (low or elevated) iron status. A gene-iron interaction was detected (likelihood-ratio test P = 0.018); however, subject numbers restricted category-specific interpretation.CONCLUSIONSIron-related genes, iron status, and their interaction predict mortality in HIV. These findings illustrate the complexity and uncertainty surrounding best practice for managing abnormal iron status and anemia during HIV infection and in regions with a high risk of infection.

Objective:To comprehensively assess iron status and determine whether elevated iron status, like anemia, predicts mortality. Methods:We followed 1362 Gambian adults (53% female) in an HIV-seroprevalent clinic-based cohort over 11.5 years to ascertain all-cause mortality. Baseline iron status (iron, soluble transferrin receptor [sTfR], transferrin, ferritin, transferrin saturation, log [transferrin receptor: ferritin]), age, gender, ethnicity, hemoglobin, body mass index, HIV type, absolute CD4 count, malaria status, and α-1-antichymotrypsin were measured. Results:The mortality rate was 25.9/100 person-years. Elevated iron universally predicted greater mortality compared to normal iron status for all iron status indices, with the exception of sTfR in unadjusted models. In fully adjusted models, transferrin (elevated vs. normal, hazard ratio [HR]: 1.77; 95% confidence interval [CI]: 1.30 to 2.42; P < 0.001), ferritin (elevated vs. normal, HR: 1.40; 95% CI: 1.07 to 1.83; P = 0.014), and the combined iron status index (highly elevated vs. normal, HR: 2.20; 95% CI: 1.16 to 4.18; P = 0.016) remained significant predictors. As expected, hemoglobin (Hb) concentration and absolute CD4 counts were each inversely associated with mortality. Conclusions:Elevated iron status predicts mortality in HIV infection, even after adjustment for immunosuppression and other confounders. This finding has implications in the clinical monitoring of disease progression and for iron-supplementation practices in areas of high HIV prevalence.

Supplementation with carotene-rich fruits may be an effective and sustainable approach to prevent vitamin A deficiency. To test the effectiveness of mango supplementation, 176 Gambian children, aged 2 to 7 y, were randomly assigned to one of four treatments: 75 g of dried mango containing approximately 150 micro g retinol activity equivalents with (MF) or without (M) 5 g of fat, 5 d/wk for 4 mo or 60,000 micro g of vitamin A (A) or placebo (P) capsule at baseline. After 4 mo, plasma beta-carotene was greater in both the M (P < 0.05) and MF (P = 0.07) groups compared with the P group. After controlling for baseline plasma retinol, elevated acute phase proteins and age, plasma retinol concentrations in the A and MF, but not M, groups were higher than in the P group at the end of the study (P < 0.01). Increases in retinol concentrations, however, were small in both groups. These results support the use of dietary supplementation with dried mangoes and a source of fat as one of several concurrent strategies that can be used to help maintain vitamin A status of children in developing countries where there is a severe seasonal shortage of carotenoid-rich foods.

Supplementation with carotene-rich fruits may be an effective and sustainable approach to prevent vitamin A deficiency. To test the effectiveness of mango supplementation, 176 Gambian children, aged 2 to 7 y, were randomly assigned to one of four treatments: 75 g of dried mango containing 150 g retinol activity equivalents with (MF) or without (M )5go ffat, 5 d/wk for 4 mo or 60,000 g of vitamin A (A) or placebo (P) capsule at baseline. After 4 mo, plasma -carotene was greater in both the M (P 0.05) and MF (P 0.07) groups compared with the P group. After controlling for baseline plasma retinol, elevated acute phase proteins and age, plasma retinol concentrations in the A and MF, but not M, groups were higher than in the P group at the end of the study (P 0.01). Increases in retinol concentrations, however, were small in both groups. These results support the use of dietary supplementation with dried mangoes and a source of fat as one of several concurrent strategies that can be used to help maintain vitamin A status of children in developing countries where there is a severe seasonal shortage of carotenoid-rich foods. J. Nutr. 132: 3693-3699, 2002.