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Background:

Histone deacetylase (HDAC), a host mediator of gene repression, inhibits HIV gene expression and virus production and may contribute to quiescence of HIV within resting CD4 T cells.

Objectives:

To test the ability of valproic acid (VPA), an inhibitor of HDAC in clinical use, to induce expression of HIV from resting CD4 T cells.

Methods:

Chromatin immunoprecipitation measured the capability of VPA to deacetylate the HIV promoter, a remodeling of chromatin linked to gene expression. The effect of VPA on resting CD4 T cell phenotype was measured by flow cytometric analysis, and its effect on de novo HIV infection of peripheral blood mononuclear cells was measured ex vivo. Outgrowth of HIV from resting CD4 T cells of aviremic, HIV-infected donors treated with highly active antiretroviral therapy was compared in limiting-dilution cultures after mitogen stimulation or exposure to VPA.

Results:

VPA induced …