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Higher Serum Iron Is Associated With Increased Oxidant Stress in HIV-Infected Men

Crist, Matthew B. MD, MPH*; Melekhin, Vlada V. MD, MPH*; Bian, Aihua MPH; Shintani, Ayumi PhD, MPH; Milne, Ginger L. PhD; Kallianpur, Asha R. MD, MPH§; Dageforde, Leigh A. MD; Haas, David W. MD*; Hulgan, Todd MD, MPH*

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 1st, 2013 - Volume 64 - Issue 4 - p 367–373
doi: 10.1097/QAI.0b013e3182a60f36
Clinical Science

Background: F2-isoprostanes (F2-IsoP) are oxidant stress biomarkers that are higher in HIV-infected women than men. We explored whether the effect of hemoglobin (Hgb), serum iron, or anemia on F2-IsoP is different between HIV-infected women and men.

Methods: Plasma F2-IsoP were quantified by gas chromatography/mass spectrometry; clinical and laboratory data were collected at enrollment or from the medical record. Multivariable linear regression was used to assess associations between F2-IsoP and Hgb, anemia as a dichotomous variable, and serum iron with adjustment for age, sex, race, body mass index, CD4+ lymphocyte count, self-reported current smoking status, and antiretroviral therapy.

Results: Compared with men, women had lower Hgb [median: 12.7 (interquartile range: 11.8–13.9) vs. 14.9 (13.7–15.8) g/dL, P < 0.001], lower iron levels [75 (47–97) vs. 90 (69–121) µg/dL, P = 0.004], more anemia (29% vs. 10%, P < 0.001), and higher levels of F2-IsoP [42 (32–62) vs. 36 (25–46) pg/mL, P < 0.001]. The relationship between iron and F2-IsoP differed significantly between men and women (interaction P = 0.02). Men had a 21% (95% confidence interval: 8 to 36) increase in F2-IsoP per interquartile increase in iron (P = 0.001), whereas no relationship was seen among women [−4% (−17 to 13, P = 0.65].

Conclusions: Although women have overall higher F2-IsoP than men, a relationship between circulating F2-IsoP and iron levels was observed in men but not in women with HIV infection. The association between female sex and higher F2-IsoP is not explained by iron or Hgb levels because the association persists when controlling for these factors. The role of iron in oxidant stress and sex-specific differences among HIV-infected individuals require further study.

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*Department of Medicine, Division of Infectious Diseases;

Department of Biostatistics;

Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN;

§Departments of Genomic Medicine and Medicine, Cleveland Clinic Foundation/Lerner Research Institute, Cleveland, OH; and

Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN (Dr Crist is now with the Acute Disease Epidemiology Section, Georgia Department of Public Health, Atlanta, GA; Dr Melekhin is now with Middle Tennessee Medical Center, Murfreesboro, TN).

Correspondence to: Matthew B. Crist, MD, MPH, Acute Disease Epidemiology Section, Georgia Department of Public Health, 2 Peachtree St, Office14-222, Atlanta, GA 30303 (e-mail:

Supported in part by research grants from Boehringer-Ingelheim Pharmaceuticals and the Bristol-Myers Squibb Company. Additional support was provided by National Institutes of Health/National Center for Complementary and Alternative Medicine grant K23 AT002508 (T.H.), National Institutes of Health/NIMH grant 1R01 MH095621 (A.R.K.), the Vanderbilt-Meharry Center for AIDS Research grant P30 AI54999 (A.S. and D.W.H.), and the Vanderbilt University School of Medicine Emphasis Program (L.A.D.). The funding agencies were not involved in data collection, analysis, or manuscript preparation. T.H. has received research funding from Merck & Co. D.W.H. has received research grants from Bavarian Nordic, Boehringer-Ingelheim, and the Bristol-Myers Squibb Company, Gilead Sciences, Merck, Tanox, and Tibotec. He is a Scientific Advisory Board member for GlaxoSmithKline. G.L.M. has provided consultancy work for Roche, United States.

The data were presented in part at IDWeek, October 17–21, San Diego, CA.

M.B.C. and V.V.M. contributed equally to the work.

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Received March 02, 2013

Accepted July 10, 2013

© 2013 by Lippincott Williams & Wilkins