Serum Citrate Levels, Haptoglobin Haplotypes and Transferrin Receptor (CD71) in Patients With HIV-1 Infection

Abstract

Background: The progression of HIV-1 infection towards its more advanced stages is accompanied by changes in iron metabolism and increased body iron stores.

Patients and Methods: Given the ability of HIV to alter iron metabolism, we studied the principal (transferrin system) and alternative (citrate system) iron pathways in a group of 65 HIV-infected patients (symptomatic stage B1–B3) and in a group of 36 healthy seronegative individuals. We determined serum citrate levels, haptoglobin (Hp) haplotypes, expression of transferrin receptor (CD71) on cell lines infected with HIV-1 as well as iron markers including blood iron, transferrin and ferritin.

Results: Our data showed decreased serum citrate levels in the HIV-infected patients compared to controls (92.9 ± 22.4 μM/l vs 126.2 ± 29.2 μM/l; p < 0.01). In particular, the serum citrate levels negatively correlated with HIV-1 RNA copy number (mean: 2.53 ± 1.88 × 10⁵/ml, r_s = 0.70, p < 0.01) and positively correlated with CD4+ T-lymphocyte count (mean: 241 ± 168/ml, r_s = 0.64, p > 0.05). Accordingly, blood iron, transferrin and red cell concentrations were lower in HIV-infected patients compared to the controls, whereas serum ferritin levels were higher in HIV-infected patients. Moreover, the Hp haplotype distribution showed significant differences only in the group of HIV-infected patients (p = 0.02; χ² test).

Conclusion: Our results show that iron metabolism is altered in patients with HIV-1 infection. The alternative pathway (citrate system) is particularly affected, since when citrate levels are low, both aconitase activity and HIV-1 replication need iron.