To the Editor:
We have recently shown that the mean number of CCR5 coreceptors at the surface of CD4+ cells strongly determines the efficiency of HIV-1 life cycle in vitro. 1 For this reason, we have tested the hypothesis that low CD4+ T-cell surface CCR5 density could favor resistance to HIV-1 infection in vivo. For this purpose, using a quantitative flow cytometry assay, 2 we measured CCR5 expression in 24 HIV-1-seronegative adults (14 men and 10 women) with multiple high-risk sexual exposures to HIV-1. Figure 1 shows that exposed uninfected subjects expressed low CCR5 densities (arithmetics means of 9273 [95% CI, 7661–10,885] CCR5 molecules per cell) compared with 84 sex-matched nonexposed control HIV-negative individuals (arithmetics means of 11,145 [95% CI, 10,379–11,911]P = 0.05).
As we have previously shown that CD4+ T-cell surface CCR5 density is stable over time for a given individual, 2 these results argue for the fact that low CCR5 expression could participate, in addition to virologic factors, to immune responses or to antiviral factors produced by CD8+ T cells in the resistance to HIV-1 infection. 3 They also explain why subjects heterozygous for the CCR5 32 base-pair deletion (Δ32) allele, who express low CCR5 densities, 4 might be more resistant to HIV-1 infection. 5,6 Moreover, our data are consistent with previous works reporting, in conflict with others, 7 that CD4+ T cells from some exposed uninfected subjects are less susceptible to HIV-1 infection 8,9 and that these CD4+ T cells show low surface expression of CCR5. 8,10
Our data further emphasize the key role played in HIV-1 infection by CD4+ T-cell surface CCR5 density, which influences in vivo infectibility (this work), virus load, 2 disease progression, 11 and response to treatment. 12
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11. Reynes J, Portales P, Segondy M, et al. CD4 T cell surface CCR5 density as a host factor in HIV-1 disease progression. AIDS. 2001; 15:1627–1634.
12. Gervaix A, Nicolas J, Portales P, et al. Response to treatment and disease progression linked to CD4+ T cell surface CCR5 density in HIV-1 vertical infection. J Infect Dis. 2002; 185:1055–1061.