Elimination of HIV-1 Latently Infected Cells by Gnidimacrin and a Selective HDAC Inhibitor.

We have previously reported gnidimacrin (GM), a protein kinase C (PKC) agonist, significantly reduces the frequency of HIV-1 latently infected cells in peripheral blood mononuclear cells (PBMCs) from patients undergoing successful antiretroviral therapy at low picomolar concentrations ex vivo , which is distinct from other latency reversing agents. In this study, we demonstrate that strong viral reactivation by GM is a mechanism for elimination of latently infected cells, and a histone deacetylase inhibitor (HDACI), a thiophenyl benzamide (TPB), further potentiated the efficacy of GM against latent HIV-1. The effect of GM on latent HIV-1 activation was potentiated by TPB in cell models by 2-3-fold. The GM/TPB combination further decreased the frequency of HIV-infected cells in latently infected patient PBMCs over 3-fold when compared with GM alone, which caused a 5-fold reduction compared with the solvent control. Thus, GM/TPB is a unique combination that may reduce latent HIV-1 reservoirs at nontoxic concentrations.