Dynamics of CD8 T-Cell Activation After Discontinuation of HIV Treatment Intensification
Por:
Massanella, M, Esteve, A, Buzon, MJ, Llibre, JM, Puertas, MC, Gatell, JM, Domingo, P, Stevenson, M, Clotet, B, Martinez-Picado, J, Blanco, J
Publicada:
1 jun 2013
Resumen:
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.
Filiaciones:
Massanella, M:
Univ Hosp Germans Trias & Pujol, Inst Invest Ciencies Salut Germans Trias & Pujol, IrsiCaixa, Inst Recerca SIDA, Badalona 08916, Barcelona, Spain
Esteve, A:
CEEISCAT ICO ASPC, Ctr Epidemiol Studies STI, Badalona, Spain
CEEISCAT ICO ASPC, HIV AIDS Catalonia, Badalona, Spain
Buzon, MJ:
Univ Hosp Germans Trias & Pujol, Inst Invest Ciencies Salut Germans Trias & Pujol, IrsiCaixa, Inst Recerca SIDA, Badalona 08916, Barcelona, Spain
Llibre, JM:
Lluita Sida Fdn, Badalona, Spain
Univ Autonoma Barcelona, Univ Hosp Germans Trias & Pujol, Badalona 08916, Barcelona, Spain
Puertas, MC:
Univ Hosp Germans Trias & Pujol, Inst Invest Ciencies Salut Germans Trias & Pujol, IrsiCaixa, Inst Recerca SIDA, Badalona 08916, Barcelona, Spain
Gatell, JM:
Hosp Clin IDIBAPS, Barcelona, Spain
Domingo, P:
Hosp Sant Pau, Barcelona, Spain
Stevenson, M:
Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA
Clotet, B:
Univ Hosp Germans Trias & Pujol, Inst Invest Ciencies Salut Germans Trias & Pujol, IrsiCaixa, Inst Recerca SIDA, Badalona 08916, Barcelona, Spain
Lluita Sida Fdn, Badalona, Spain
Univ Autonoma Barcelona, Univ Hosp Germans Trias & Pujol, Badalona 08916, Barcelona, Spain
Martinez-Picado, J:
Univ Hosp Germans Trias & Pujol, Inst Invest Ciencies Salut Germans Trias & Pujol, IrsiCaixa, Inst Recerca SIDA, Badalona 08916, Barcelona, Spain
ICREA, Barcelona, Spain
Blanco, J:
Univ Hosp Germans Trias & Pujol, Inst Invest Ciencies Salut Germans Trias & Pujol, IrsiCaixa, Inst Recerca SIDA, Badalona 08916, Barcelona, Spain
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