Are Plasma Biomarkers of Immune Activation Predictive of HIV Progression: A Longitudinal Comparison and Analyses in HIV-1 and HIV-2 Infections?

作者：Nyamweya Samuel^*; Townend John; Zaman Akram; Steele Sarah Jane; Jeffries David; Rowland Jones Sarah; Whittle Hilton; Flanagan Katie L; Jaye Assan

来源：PLos One, 2012, 7(9): e44411.

DOI：10.1371/journal.pone.0044411

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 beta-2 microglobulin (beta-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 beta-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 beta-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 beta-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.

• 出版日期2012-9-10