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. Copyright © 2013 by Lippincott Williams & Wilkins.
Original language | English |
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Pages (from-to) | 152-160 |
Journal | Journal of acquired immune deficiency syndromes (1999) |
Volume | 63 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1 Jun 2013 |
Keywords
- CD38
- HIV-1 eradication
- HIV-1 integrase
- Viral Reservoir