Dynamics of CD8 T-cell activation after discontinuation of HIV treatment intensification

Marta Massanella, Anna Esteve, Maria J. Buzón, Josep M. Llibre, Maria C. Puertas, Josep M. Gatell, Pere Domingo, Mario Stevenson, Bonaventura Clotet, Javier Martinez-Picado, Julià Blanco

Research output: Contribution to journalArticle

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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-LTR2 (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-LTR2 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 CD45RA2 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 CD45RA2 CD4 T-cell redistribution in intensified individuals may reflect residual viral replication during apparently suppressive HAART.

Original languageEnglish
Pages (from-to)152-160
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume63
Issue number2
DOIs
StatePublished - Jun 1 2013

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HIV
T-Lymphocytes
Highly Active Antiretroviral Therapy
Therapeutics
HIV-1
Linear Models
Plasmids
Complementary DNA
Raltegravir Potassium

Keywords

  • CD38
  • HIV-1 eradication
  • HIV-1 integrase
  • Viral Reservoir

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Medicine(all)

Cite this

Massanella, M., Esteve, A., Buzón, M. J., Llibre, J. M., Puertas, M. C., Gatell, J. M., ... Blanco, J. (2013). Dynamics of CD8 T-cell activation after discontinuation of HIV treatment intensification. Journal of Acquired Immune Deficiency Syndromes, 63(2), 152-160. https://doi.org/10.1097/QAI.0b013e318289439a

Dynamics of CD8 T-cell activation after discontinuation of HIV treatment intensification. / Massanella, Marta; Esteve, Anna; Buzón, Maria J.; Llibre, Josep M.; Puertas, Maria C.; Gatell, Josep M.; Domingo, Pere; Stevenson, Mario; Clotet, Bonaventura; Martinez-Picado, Javier; Blanco, Julià.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 63, No. 2, 01.06.2013, p. 152-160.

Research output: Contribution to journalArticle

Massanella, M, Esteve, A, Buzón, MJ, Llibre, JM, Puertas, MC, Gatell, JM, Domingo, P, Stevenson, M, Clotet, B, Martinez-Picado, J & Blanco, J 2013, 'Dynamics of CD8 T-cell activation after discontinuation of HIV treatment intensification', Journal of Acquired Immune Deficiency Syndromes, vol. 63, no. 2, pp. 152-160. https://doi.org/10.1097/QAI.0b013e318289439a
Massanella, Marta ; Esteve, Anna ; Buzón, Maria J. ; Llibre, Josep M. ; Puertas, Maria C. ; Gatell, Josep M. ; Domingo, Pere ; Stevenson, Mario ; Clotet, Bonaventura ; Martinez-Picado, Javier ; Blanco, Julià. / Dynamics of CD8 T-cell activation after discontinuation of HIV treatment intensification. In: Journal of Acquired Immune Deficiency Syndromes. 2013 ; Vol. 63, No. 2. pp. 152-160.
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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-LTR2 (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-LTR2 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 CD45RA2 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 CD45RA2 CD4 T-cell redistribution in intensified individuals may reflect residual viral replication during apparently suppressive HAART.",
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