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Current Trends in Immunology   Volumes    Volume 2 
Abstract
Immune reconstitution during highly active antiretroviral therapies
Guislaine Carcelain, Taisheng Li, Guy Gorochov, Marc Renaud, Catherine Blanc, Brigitte Autran, Patrice Debré
Pages: 87 - 97
Number of pages: 11
Current Trends in Immunology
Volume 2 

Copyright © 1999 Research Trends. All rights reserved

ABSTRACT

HIV infection induces CD4 T cell defects that include a quantitative CD4 T cells depletion and a loss of T helper function leading to a progressive immune deficiency. Advances in potent antiretroviral therapy allowed both a qualitative and quantitative improvement of T cell abnormalities. Early report indicated that monotherapy with protease inhibitors which reduced plasma-viremia only transiently, resulted in a CD4 T cell increase with a limited benefit for T cell function: a slight improvement  in memory  CD4+ T cell responses to recall antigens was only observed when detectable prior to the onset of therapy. More recently combined drugs regimens commonly described as Highly Active Antiretroviral Therapies (HAART) stably reduced virus replication and reversed the major CD4 T cell abnormalities for extended periods of time. As first shown by our groups such improvement includes: 1) a rapid rise in CD4 and CD8 T cells followed by a slower CD4 cell increase while the CD8 counts were decreasing towards baseline value; 2) a rapid increase in memory CD4 T cells during the first month of treatment followed by a late increase in naïve T cells coexpressing CD45RA 62L molecules after 6 months of efficient antiviral treatment; 3) a significant reduction of CD4 and CD8 activation markers in parallel to plasma virus load reduction ; 4) a restoration in CD4 T cell reactivity to recall antigens ; 5) normalization of the CD4 and CD8 repertoire as studied by the distribution of CDR3 lengths. These observations open new perspectives for the understanding of CD4+ T cell deficiency, clinical management and therapeutic strategies of HIV infection. In the present review we will envisage past and present immunological results obtained with HAART and some of the questions raised by immune restoration in patients treated at advanced stages of the disease.

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