Higher serum iron is associated with increased oxidant stress in HIV-infected men

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.

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.

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].

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.