title: Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections?
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Medical Research Council UK, Banjul, The Gambia, West Africa.
authors.forename: Samuel
authors.initials: S
authors.lastname: Nyamweya
authors.forename: John
authors.initials: J
authors.lastname: Townend
authors.forename: Akram
authors.initials: A
authors.lastname: Zaman
authors.forename: Sarah Jane
authors.initials: SJ
authors.lastname: Steele
authors.forename: David
authors.initials: D
authors.lastname: Jeffries
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D015498:HIV-2 / Q000302:isolation & purification*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D019798:Neopterin / Q000097:blood; D019562:Viral Load; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D015415:Biomarkers; D001613:beta 2-Microglobulin; D019798:Neopterin