Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections?
| Autor: | David Jeffries, Samuel Nyamweya, Sarah Rowland-Jones, Sarah Jane Steele, Akram Zaman, Assan Jaye, Katie L. Flanagan, John Townend, Hilton Whittle |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Epidemiology lcsh:Medicine HIV Infections Pathogenesis chemistry.chemical_compound Pathology Longitudinal Studies lcsh:Science Immune Response Multidisciplinary Neopterin Viral Load HIV epidemiology Cohort Disease Progression Biomarker (medicine) Medicine Infectious diseases Female Viral load Research Article Adult Immunology Enzyme-Linked Immunosorbent Assay Viral diseases Biology Immune Activation Median follow-up Diagnostic Medicine Humans Beta-2 microglobulin lcsh:R Immunity HIV CD4 Lymphocyte Count Biomarker Epidemiology chemistry SuPAR Immune System HIV-2 HIV-1 lcsh:Q Clinical Immunology beta 2-Microglobulin Biomarkers General Pathology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 9, p e44411 (2012) |
| ISSN: | 1932-6203 |
| Popis: | BACKGROUND: Chronic immune activation is a hallmark of HIV infection and has been associated with disease progression. Assessment of soluble biomarkers indicating immune activation provide clues into pathogenesis and hold promise for the development of point-of-care monitoring of HIV in resource-poor-settings. Their evaluation in cohort resources is therefore needed to further their development and use in HIV research. METHODOLOGY/PRINCIPAL FINDINGS: Longitudinal evaluation of βeta-2 microglobulin (β-2 m), neopterin and suPAR soluble urokinase-type plasminogen activator receptor (suPAR) was performed with archived plasma samples to predict disease progression and provided the first direct comparison of levels in HIV-1 and HIV-2 infections. At least 2095 samples from 137 HIV-1 and 198 HIV-2 subjects with starting CD4% of ≥ 28 and median follow up of 4 years were analysed. All biomarkers were correlated negatively to CD4% and positively to viral load and to each other. Analyses in subjects living for ≥ 5 years revealed increases in median β-2 m and neopterin and decreases in CD4% over this period and the odds of death within 5 years were positively associated with baseline levels of β-2 m and neopterin. ROC analyses strengthened the evidence of elevation of biomarkers in patients approaching death in both HIV-1 and HIV-2 infections. Regression models showed that rates of biomarker fold change accelerated from 6-8 years before death with no significant differences between biomarker levels in HIV-1 and HIV-2 at equal time points prior to death.An 'immune activation index' analysis indicative of biomarker levels at equivalent viral loads also showed no differences between the two infections. CONCLUSIONS/SIGNIFICANCE: Our results suggest that β-2 m and neopterin are useful tools for disease monitoring in both HIV-1 and HIV-2 infections, whereas sUPAR performed less well. Levels of immune activation per amount of virus were comparable in HIV-1 and HIV-2 infected subjects. |
| Databáze: | OpenAIRE |
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