Haptoglobin polymorphism, iron metabolism and mortality in HIV infection.
BACKGROUND
Three phenotypes of the antioxidant protein haptoglobin are known: Hp 1-1, Hp 2-1 and Hp 2-2.


OBJECTIVE
To investigate the outcome of HIV infection according to haptoglobin type.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Delanghe
J R
JR
Department of Clinical Chemistry, Microbiology and Immunology, University Hospital, Gent, Belgium.
Langlois
M R
MR
Boelaert
J R
JR
Van Acker
J
J
Van Wanzeele
F
F
van der Groen
G
G
Hemmer
R
R
Verhofstede
C
C
De Buyzere
M
M
De Bacquer
D
D
Arendt
V
V
Plum
J
J
D000328:Adult; D001205:Ascorbic Acid / Q000097:blood; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000235:genetics / Q000401:mortality / Q000821:virology; D006242:Haptoglobins / Q000145:classification / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D018384:Oxidative Stress; D010641:Phenotype; D011110:Polymorphism, Genetic; D017741:Survivors; D019562:Viral Load
D006242:Haptoglobins; D007501:Iron; D001205:Ascorbic Acid