Dynamics of CD8 T-Cell Activation After Discontinuation of HIV Treatment Intensification

Dynamics of CD8 T-Cell Activation After Discontinuation of HIV Treatment Intensification

Online publication: 01/06/2013

Abstract:

 Background: Detection of episomal HIV cDNA has been associated with greater levels of CD8 and CD4 T-cell activation in HIV-1-infected highly active antiretroviral therapy (HAART)-suppressed individuals. However, HAART intensification exclusively reduced CD8 T-cell activation. Methods: We evaluated activation markers 12 weeks after raltegravir withdrawal in a previously described 48-week raltegravir intensification study. The subjects (n = 34) were subgrouped into 2-LTR+ (n = 12) or 2-LTR− (n = 22) subgroups according to delectability of 2-LTR episomes during the intensification period. Results: The initial differences in CD8 T-cell activation between subgroups were lost after intensification. Linear mixed models revealed significant reductions in CD8 T-cell activation in both 2-LTR− and 2-LTR+ subgroups, suggesting that raltegravir impacts subjects irrespective of 2-LTR detection. Remarkably, a partial rebound in CD8 activation markers after raltegravir discontinuation was observed in the 2-LTR+ subgroup. This restored the differences between subgroups observed at study entry, particularly in terms of CD38 expression within CD8 memory T-cells. Conversely, CD4 T-cell activation remained unchanged in both subgroups during the study period, although an early and transient CD45RA− CD4 T-cell redistribution from tissues was apparent. Conclusions: CD8 T-cell activation undergoes reversible changes during raltegravir intensification and discontinuation in patients showing detectable 2-LTR circles. The general decrease in CD8 T-cell activation and a transient CD45RA− CD4 T-cell redistribution in intensified individuals may reflect residual viral replication during apparently suppressive HAART.

Authors: Massanella, Marta PhD*; Esteve, Anna PhD†; Buzón, Maria J. PhD*; Llibre, Josep M. MD‡; Puertas, Maria C. PhD*; Gatell, Josep M. MD§; Domingo, Pere MD‖; Stevenson, Mario PhD¶; Clotet, Bonaventura MD*,‡; Martinez-Picado, Javier PhD*,#; Blanco, Julià PhD*; the IntegRal Collaborative Group *IrsiCaixa, Institut de Recerca de la SIDA, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain (M. J. Buzón is now with Infectious Disease Division, Massachusetts General Hospital, and Ragon Institute, of MGH, MIT, and Harvard. Boston, MA); †Center for Epidemiological Studies on STI and HIV/AIDS of Catalonia, CEEISCAT-ICO-ASPC, Badalona, Spain; ‡"Lluita contra la SIDA" Foundation and University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain; §Hospital Cli[Combining Acute Accent]nic-Idibaps, Barcelona, Spain; ‖Hospital Sant Pau, Barcelona, Spain; ¶Department of Medicine, University of Miami Miller School of Medicine, Miami, FL; and #ICREA, Barcelona, Spain. Read abstract online in Journal of AIDS JAIDS
  • Doi Code: doi: 10.1097/QAI.0b013e318289439a

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