Haptoglobin polymorphism, iron metabolism and mortality in HIV infection

• Published in: AIDS (London) Vol. 12; no. 9; pp. 1027 - 1032
• Main Authors: DELANGHE, J. R, LANGLOIS, M. R, ARENDT, V, PLUM, J, BOELAERT, J. R, VAN ACKER, J, VAN WANZEELE, F, VAN DER GROEN, G, HEMMER, R, VERHOFSTEDE, C, DE BUYZERE, M, DE BACQUER, D
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 18-06-1998
• Subjects: Adult; AIDS/HIV; Ascorbic Acid - blood; Biological and medical sciences; CD4 Lymphocyte Count; Female; Haptoglobins - classification; Haptoglobins - genetics; HIV Infections - blood; HIV Infections - genetics; HIV Infections - mortality; HIV Infections - virology; Human viral diseases; Humans; Infectious diseases; Iron - blood; Male; Medical sciences; Oxidative Stress; Phenotype; Polymorphism, Genetic; Survivors; Viral diseases; Viral hepatitis; Viral Load; Human; Immunopathology; Prognosis; Mortality; AIDS; Iron; Metabolism; Immune deficiency; Infection; Phenotype; Haptoglobin; Viral disease; Risk factor; Serum; Polymorphism
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-199809000-00010

Three phenotypes of the antioxidant protein haptoglobin are known: Hp 1-1, Hp 2-1 and Hp 2-2.
To investigate the outcome of HIV infection according to haptoglobin type.
Haptoglobin phenotypes were determined using starch gel electrophoresis in serum obtained from 653 HIV-infected Caucasians in the AIDS reference centers of Gent (n = 184), Antwerp (n = 309), and Luxembourg (n = 160). Survival was compared between haptoglobin types using Kaplan-Meier curves. Plasma HIV-1 RNA was quantified by reverse transcriptase PCR. Serum iron, transferrin saturation, ferritin, and vitamin C were assayed to evaluate iron-driven oxidative stress in 184 HIV-infected patients and 204 controls.
The haptoglobin type distribution amongst the patients (17.6% Hp 1-1, 49.9% Hp 2-1, 32.5% Hp 2-2) corresponded to that of the controls. Kaplan-Meier curves showed a higher mortality for the Hp 2-2 group (P = 0.0001; adjusted mortality risk ratio, 1.78; 95% confidence interval, 1.25-2.54). Median survival time was 11.0 years (Hp 1-1 and Hp 2-1) versus 7.33 years (Hp 2-2). Plasma HIV-1 RNA levels prior to antiviral therapy and their increase over 1 year were highest in Hp 2-2 patients (P = 0.03 and 0.003, respectively). The Hp 2-2 type was associated with higher serum iron, transferrin saturation, and ferritin levels and with low vitamin C concentrations. Furthermore, ferritin concentrations were higher in HIV-infected patients than in controls (P < 0.0001).
HIV-infected patients carrying the Hp 2-2 phenotype show a worse prognosis, which is reflected by a more rapid rate of viral replication (in the absence of antiviral treatment). They also accumulate more iron and oxidize more vitamin C, suggesting that less efficient protection against haemoglobin/iron-driven oxidative stress may be a direct mechanism for stimulating viral replication.