resminostat and HIV-Infections

The presence of T cell reservoirs in which human immunodeficiency virus (HIV) establishes latency by integrating into the host genome represents a major obstacle to an HIV cure and has prompted the development of strategies aimed at the eradication of HIV from latently infected cells. The "shock-and-kill" strategy is one of the most pursued approaches to the elimination of viral reservoirs. Although several latency-reversing agents (LRAs) have shown promising reactivation activity, they have failed to eliminate the cellular reservoir. In this study, we evaluated a novel immune system-mediated approach to clearing the HIV reservoir, based on a combination of innate immune stimulation and epigenetic reprogramming. The combination of the STING agonist cGAMP (cyclic GMP-AMP) and the FDA-approved histone deacetylase inhibitor resminostat resulted in a significant increase in HIV proviral reactivation and specific apoptosis in HIV-infected cells

Topics: CD4-Positive T-Lymphocytes; Epigenesis, Genetic; Gene Expression Regulation, Viral; Histone Deacetylase Inhibitors; HIV Infections; HIV-1; Humans; Hydroxamic Acids; Immunity, Innate; Leukocytes, Mononuclear; Sulfonamides; Virus Activation; Virus Latency; Virus Replication