Despite the fact that HDAC inhibitors
often increase gene expression, ITF2357
did not increase CCR5 surface expression
on CD4+ T cells (39). It would be counterproductive
if agents stimulating the latent
virus upregulated CCR5 and CXCR4 surface
expression. In fact, surface expression
of CXCR4 on CD4+ T cells and CCR5 on
monocytes was reduced by 50% by
ITF2357 (39). Consistent with decreasing
coreceptor surface expression, ITF2357 reduced
steady-state mRNA levels of
CXCR4 and CCR5 in peripheral blood
mononuclear cells (PBMCs), as measured
by reverse transcriptase–polymerase chain
reaction (RT-PCR) and by Affimetrix gene
expression, respectively. Thus, in a clinical trial of givinostat in HIV-1-infected
patients, this property of givinostat may
also reduce any reinfection of naive CD4+
T cells.