CD4 T cell surface CCR5 density as a host factor in HIV-1 disease progression

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Abstract
We have recently shown that the number of CCR5 molecules at the surface of peripheral blood CD4 T cells (CCR5 density) correlates with the viral RNA plasma level in HIV-1-infected individuals. As viral load is a strong predictor of outcome in HIV infection, the present study examines the correlation between CCR5 density and HIV-1 disease progression. Using a quantitative flow cytometry assay, we measured CCR5 density in HIV-1-infected adults and control healthy volunteers. The CCR5 genotype (presence of a Δ32 allele) was also determined. CCR5 density was stable over time on non-activated, HLA-DR−CD4 T cells of infected individuals. In a study cohort of 25 patients, asymptomtic and non-treated, we observed a correlation between CCR5 density on HLA-DR−CD4 T cells and the CD4 T cell slope (P = 0.026), which was independent of the presence or absence of the Δ32CCR5 deletion. In particular, slow progressors expressed lower CCR5 densities than non-slow progressors (P = 0.004) and non-infected control subjects (P = 0.002). These results are compatible with the hypothesis that CCR5 density, which is a key factor of HIV-1 infectability, determines in-vivo HIV production, and thereby the rate of CD4 cell decline. Consequently, CCR5 density quantitation could be a new valuable prognostic tool in HIV-1 infection. Moreover, these data emphasize the therapeutic potential of treatments that reduce functional CCR5 density.