A study of four markers of immune activation and disease progression: a comparison between HIV-1 and HIV-2 infection

Lead Research Organisation: MRC Unit, The Gambia

Abstract

Infection with the HIV germ (virus) that causes AIDS is accompanied with massive activation of the bodys defence system. When this activation happens over a long time it causes exhaustion of all the defence systems of the body. This germ causes massive death to the cells that defend the body against infections (CD4) through this intense activation. The measurement of the levels of soluble chemicals that arise from this activation has been shown to be easy to perform and may be better predictor of the progression of disease in HIV infection to AIDS status than the conventional CD4 counts and measurement of the levels of virus circulating in the blood. This study therefore aims to measure and compare four soluble chemicals in the body that indicate the levels of chronic activation of the defence system in HIV-1 and HIV-2 infected subjects. These chemicals are named as: neopterin, beta 2-microglobulin, lipolysaccharide and suPAR all of which have been shown to be increased in HIV infected compared to uninfected individuals. This comparison will make us understand better the role of intense activation in making HIV-infected patients to deteriorate during the course of their illness.

Technical Summary

There is still insufficient explanation as to how HIV causes profound loss of CD4 T cells, despite only a small proportion of cells being infected. Recent reports suggest a massive loss of CD4 from the gut early in infection which has been attributed largely to immune activation. Chronic immune activation, which is a hallmark of HIV infection, is therefore thought to partly account for the CD4 T cell depletion and immune dysfunction. Indeed, immune activation has been suggested as a stronger predictive factor for disease progression in HIV than the conventional CD4 counts and viral load. The soluble immune activation biomarkers neopterin, beta 2-microglobulin (beta 2-M), lipopolysaccharide (LPS) and soluble urokinase plasminogen activator receptor (suPAR) have all been shown to be upregulated in HIV compared to uninfected individuals. The levels are significantly higher in advanced cases (symptomatic phase) than early in the course of infection (asymptomatic phase). This study proposes to evaluate in a head to head comparison the levels of immune activation markers using retrospective stored plasma samples from HIV-1 and HIV-2 positive individuals in the Fajara HIV Cohort. A comprehensive evaluation of immune activation markers in disease progressing and non-progressing individuals will provide clues as to how HIV causes disease.
 
Description HIV Research Trust, UK (www.hivresearchtrust.org.uk)
Amount £10,000 (GBP)
Organisation HIV Research Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2009 
End 12/2009
 
Description HIV Research Trust-UK ( www.hivresearchtrust.org.uk)
Amount £10,000 (GBP)
Organisation HIV Research Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2009 
End 01/2010