CCR5 density on CD4 cells governs course of HIV infection in children
The density of CC chemokine receptor 5 (CCR5) molecules on the surface of inactivated CD4 cells correlates with disease progression and with treatment response in children vertically infected with HIV.
Development of therapy to reduce CCR5 density could therefore be expected to slow disease progression and increase response to treatment, a team of French and Swiss investigators suggests.
Dr Pierre Corbeau, of the Hôpital Saint Eloi in Montpellier, France, and associates monitored the density of CCR5 molecules on CD4 cells in 22 HIV-infected children for 12 months. As reported in The Journal of Infectious Diseases for April 15, the density remained stable over time.
Among 35 therapy-naïve children, aged 10 to 201 months, the CCR5 density was correlated with severity of disease according to clinical and biologic stage (p < 0.001) and annual percentage of CD4 cell loss (p = 0.034). CD4 cell loss was dramatically increased when CCR5 density exceeded 10,000 molecules per cell.
The CCR5 density was also associated with the drop in viral load among 21 children who initiated treatment with two nucleoside inhibitors and one protease inhibitor (p = 0.026).
Dr Corbeau’s team theorises that viral replication is more difficult to block when cells express high densities of CCR5 molecules. Specifically, “In high CCR5 expressers, low residual viremia will result in the productive infection of cells with a high density of membrane CCR5, and replication will be sustained.”
The authors conclude that determination of CCR5 density could aid in determining prognosis and in decision-making regarding treatment.
Corbeau P, Eliaou JF, Astruc J, et al. Response to Treatment and Disease Progression Linked to CD4+ T Cell Surface CC Chemokine Receptor 5 Density in Human Immunodeficiency Virus Type 1 Vertical Infection. J Infect Dis 2002 Apr 15;185(8):1055-61
Source: Reuters Health