Haptoglobin polymorphism, iron metabolism and mortality in HIV infection
| Autor: | Joris R. Delanghe, Michel R. Langlois, Johan R. Boelaert, Jos Van Acker, Filip Van Wanzeele, Guido van der Groen, Robert Hemmer, Chris Verhofstede, Marc De Buyzere, Dirk De Bacquer, Vic Arendt, Jean Plum |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Adult
Male medicine.medical_specialty Opportunistic infection Iron Immunology HIV Infections Ascorbic Acid Oropharyngeal Candidiasis Oral administration Internal medicine medicine Immunology and Allergy Humans Survivors Mycosis Polymorphism Genetic Haptoglobins business.industry Viral Load medicine.disease CD4 Lymphocyte Count Clinical trial Regimen Oxidative Stress Infectious Diseases Phenotype Oral microbiology Female business Fluconazole medicine.drug |
| Zdroj: | AIDS (London, England). 12(9) |
| ISSN: | 0269-9370 |
| Popis: | 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 (P0.0001).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. |
| Databáze: | OpenAIRE |
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