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

Abstract

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. 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. 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. 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.