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


METHODS
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 Delta 32 allele) was also determined.


RESULTS
CCR5 density was stable over time on non-activated, HLA-DR(-)CD4 T cells of infected individuals. In a study cohort of 25 patients, asymptomatic 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 Delta 32CCR5 deletion. In particular, slow progressors expressed lower CCR5 densities than non-slow progressors (P = 0.004) and non-infected control subjects (P = 0.002).


CONCLUSIONS
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.
Reynes
J
J
Service des Maladies Infectieuses et Tropicales, Hôpital Gui de Chauliac, Montpellier, France.
Portales
P
P
Segondy
M
M
Baillat
V
V
André
P
P
Avinens
O
O
Picot
M C
MC
Clot
J
J
Eliaou
J F
JF
Corbeau
P
P
D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*
D019713:Receptors, CCR5