Elevated iron status strongly predicts mortality in West African adults with HIV 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 alpha]-(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.