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JAC Advance Access published online on July 1, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg295
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Original article

Apoptosis and proliferation kinetics of T cells in patients having experienced antiretroviral treatment interruptions

Pierre-Marie Roger 1 , Jacques Durant 1 , Michel Ticchioni 2 , Philippe Halfon 3 , Jean-Philippe Breittmayer 2 , Christelle Brignone 2 , Sylvie Chaillou 1 , Brigitte Dunais 1 , Pierre Dellamonica 1 , and Alain Bernard 2

1 Service des Maladies Infectieuses et Tropicales, Hôpital de l'Archet 1, Centre Hospitalo-Universitaire de Nice, BP3079, 06202, Nice cedex 3
2 Unité INSERM 343, Centre Hospitalo-Universitaire de Nice, Hôpital de l'Archet 1, BP3079, 06202, Nice cedex 3
3 Alphabio, Marseille, France

Received 12 December 2002 ; revised 22 April 2003 ; accepted 22 April 2003

Abstract

Multiple failures of antiretroviral treatments, as a result of multidrug-resistant virus, have led to a proposal for structured therapeutic interruptions (STI). However, a significant decrease in CD4+ T cells may occur. The aim of our study was to determine the kinetics of T cell subpopulation changes, T cell apoptosis and peripheral blood mononuclear cell proliferation after STI. The impact of resistance mutation disappearance on T cell apoptosis was also studied. Ten patients were enrolled prospectively, and blood sampling was performed at weeks 0, 2, 4, 6, 8 and 12. The mean increase in viral load was 1.3 log10 copies/mL, ranging from 0.1 to 3.2. CD4+ T cell count decreased to a mean of 80 cells/mm3 from baseline to week 12. In the same period, CD8+ T cells decreased to a mean of 139 cells/mm3 . A significant increase in both T cell apoptosis and proliferation of mononuclear cells was observed. However, proliferation was an early and brief event. The increase in CD4+ T cell apoptosis was obvious in patients exhibiting complete reversion of resistance mutations to antiviral drugs. Our results suggest that during STI, apoptosis is an overwhelming phenomenon compared with proliferation, and may explain the limited immunological impact of this therapeutic option.

Keywords: apoptosis, proliferation, HIV infection, therapeutic interruption
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