[151] CD4+ T-CELL SURFACE CCR5 DENSITY IS A PREDICTIVE FACTOR OF HIV REBOUND AFTER ANTIRETROVIRAL TREATMENT INTERRUPTION

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] CD4+ T-CELL SURFACE CCR5 DENSITY IS A PREDICTIVE FACTOR OF HIV REBOUND AFTER ANTIRETROVIRAL TREATMENT INTERRUPTION

[AUTHOR(S):] P Portales¹, V Baillat², C Merle de Boever², V Lemoing², J Clot¹, J Reynes² and P Corbeau^1,3
¹Laboratoire d’Immunologie de l’Hôpital Saint Eloi; ²Service des Maladies Infectieuses et Tropicales de l’Hôpital Gui de Chauliac; and ³Institut de Génétique Humaine CNRS UPR1142, Montpellier, France

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No.
Antiviral Therapy 2003; 8(Suppl. 1):S

[ABSTRACT:] Discontinuation of highly active antiretroviral therapy (HAART) improves virological control and specific immunity in some HIV-1- infected persons, whereas on the contrary it may result in rapid viral rebound and decrease in antiviral cytotoxic T cell activity in others. The host factors responsible for these opposite consequences are largely unknown. We have previously shown that the mean number of CCR5 coreceptors at the surface of CD4+ T cells (CCR5 density) is logarithmicly correlated with viral load and disease progression during HIV-1 infection. We have explained this link by showing in vitro that CCR5 density strongly determines the efficiency of HIV-1 life cycle (Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15590-5). For this reason we assumed that CCR5 density, that is stable over time in a given individual, but varies among individuals, might determine the intensity of viral rebound after HAART cessation. To test this hypothesis, we determined by quantitative flow cytometry CCR5 density on peripheral blood CD4+ T cells of 19 chronically infected subjects (12 men and seven women, CD4 cell count ranging from 289–1739 cells/µl, HIV-1 RNA plasma level below 200 copies/ml) who stopped antiretroviral multitherapy, and measured their virus load at day 30 after HAART discontinuation. We observed a strong logarithmic correlation (r=0.709, P<0.001) between CCR5 expression and HIV-1 RNA plasma level at day 30. Interestingly, beyond a threshold of 8,000 CCR5 molecules per CD4+ T cell, virus load rebounded above 100,000 copies/ml. These results emphasize the role of CCR5 density in in vivo HIV-1 replication. Moreover, they point out CCR5 density as a predictive factor of the effect of treatment interruption, which should be reserved for patients expressing low CCR5 densities.

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