Comparison of T lymphocyte kinetics in HIV-1 and HIV-2 infections

Lead Research Organisation: MRC Unit, The Gambia

Abstract

There are two types of germs causing AIDS: HIV-1 and HIV-2. HIV-2, found mainly in West Africa does not seem to cause AIDS as quickly or as frequently as HIV-1. To explain the difference, this study aims to find out if HIV-2 is less harmful because it destroys less cells that fight infection or because the HIV-2 infected subject is able to replace them better. Understanding this may help scientists make better treatments for HIV-2 infection.||This will be done by giving the study subjects a special sugar drink (over a 10hr period of admission) which allows us to tell the difference between new and old cells on a blood test afterwards. The samples will be processed in the laboratory and the measurements of the different cells will give us a picture of how HIV-1 or HIV-2 affects them on a continuous basis. Analysis of the measurements may help explain the clinical differences between HIV-1 and HIV-2 infections.

Technical Summary

HIV-2 infected individuals survive longer and have a more protracted stable CD4 T cell count than those infected with HIV-1. Studies in our laboratory have shown that both infections exhibit similar levels of cell mediated immune responses, when matched at high CD4 T cell count, but quality of effector functional responses are superior in HIV-2 infection, probably accounting for its lower viral replication. The difference in immunological and clinical course of HIV-1 and HIV-2 infections is likely to be related to the interaction of the virus and the survival of lymphocyte subpopulations. We hypothesise that, in HIV-2 infection, there is either less marked destruction of CD4 cells or an enhanced ability to replace lost CD4 cells. Destruction would be less marked if immune activation had less impact on proliferation rates; this would be expected to allow greater preservation of naove CD4 T cells. Alternatively, in HIV-2, lost cells may be replaced more efficiently. We will investigate this by comparing proliferation and disappearance rates of naove and memory T lymphocytes in 20 HIV-2 with 20 HIV-1 infected subjects, matched for CD4 count, and in healthy sero-negative controls. This will be performed by measuring the kinetics of incorporation of deuterium from orally administered deuterated glucose into DNA of lymphocyte subpopulations. We will relate such measurements to markers of activation (HLA-DR, CD38, CD69) and proliferation (nuclear antigen Ki67).
 
Description EDCTP Senior Fellowship
Amount € 200,000 (EUR)
Organisation Sixth Framework Programme (FP6) 
Department European and Developing Countries Clinical Trials Partnership
Sector Public
Country European Union (EU)
Start 11/2012 
End 10/2014
 
Description HIV T cell kinetics studies-St Georges Hospital, UK 
Organisation St George's University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution - We provided the idea for the study and the patients -We did the immunology work
Collaborator Contribution Analyses of samples by mass Spectrophotometry
Impact A scientific paper is being drafted
Start Year 2009