Journal of Clinical Virology 20 (2001) 111 – 115 Iron status and the outcome of HIV infection: an overview Victor R. Gordeuk a, *, Joris R. Delanghe b , Michel R. Langlois b , Johan R. Boelaert c a Center for Sickle Cell Disease and Department of Medicine, Howard Uniersity College of Medicine, Washington, DC 20059, USA b Uniersity of Gent, Gent, Belgium c A.Z. St Jan, Brugge, Belgium Abstract Background: Theoretical considerations and experiments in the laboratory suggest that excessive iron stores may have an adverse effect on immunity. If so, high iron stores might be especially a problem in patients with human immunodeficiency virus (HIV) infection. Objectie and study design: Review published clinical studies that provide information regarding the effect of iron status on the outcome of HIV infection. Results: Four clinical observations have provided some perspective on the effect of iron status on the outcome of HIV-1 infection. First, in a restrospective study of HIV-positive thalassemia major patients, the rate of progression of HIV disease was significantly faster in patients with lower doses of desferrioxamine and higher serum ferritin concentrations. Second, the inadvertent simultaneous administration of low doses of oral iron with dapsone for the prophylaxis of Pneumocystis carinii pneumonia in HIV-positive patients may have been associated with excess mortality. Third, a study of haptoglobin polymorphisms in HIV-positive subjects indicated that the haptoglobin 2-2 polymorphism is associated with higher iron stores and shortened survival as compared with the haptoglobin 1-1 or 2-1 phenotypes. Fourth, a retrospective study of bone marrow macrophage iron in HIV-positive patients suggested that survival is shorter with high iron stores. Conclusion: These four observations raise the possibility that high iron status may adversely influence the outcome of HIV-1 infection. © 2001 Elsevier Science B.V. All rights reserved. Keywords: HIV; Outcome of HIV infection; Iron www.elsevier.com/locate/jcv 1. Introduction Theoretical considerations and experiments in the laboratory suggest that excessive iron stores may have an adverse effect on immunity. Cellular iron homeostasis is important in immune function (Means and Krantz, 1992), and both iron defi- ciency and iron overload seem to exert subtle effects on the immune system by altering the proliferation of T-lymphocytes and B-lymphocyte (Brock, 1994; Weiss et al., 1995). Iron plays a critical role in macrophage-mediated cytotoxicity by catalyzing the production of reactive oxygen species within the phago-lysosome (Halliwell et al., 1992; Rosen et al., 1995). * Corresponding author. 1386-6532/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved. PII:S1386-6532(00)00134-7