The study by Archin et al. investigates the administration of vorinostat (VOR), a histone deacetylase (HDAC) inhibitor, to disrupt HIV-1 latency in patients on antiretroviral therapy (ART). Despite ART, HIV-1 latency remains a significant barrier to curing the infection. The researchers isolated resting CD4+ T cells from patients with fully suppressed viremia and tested the effect of VOR. In eight patients, a single dose of VOR increased biomarkers of cellular acetylation and induced a mean 4.8-fold increase in HIV RNA expression in resting CD4+ cells. This is the first demonstration that HDAC inhibitors can therapeutically target HIV latency, providing proof-of-concept for this class of drugs as a new therapeutic approach to eradicate HIV infection. The study also highlights the need for further research to optimize dosing regimens and assess the safety and efficacy of HDAC inhibitors in targeting latent proviral genomes.The study by Archin et al. investigates the administration of vorinostat (VOR), a histone deacetylase (HDAC) inhibitor, to disrupt HIV-1 latency in patients on antiretroviral therapy (ART). Despite ART, HIV-1 latency remains a significant barrier to curing the infection. The researchers isolated resting CD4+ T cells from patients with fully suppressed viremia and tested the effect of VOR. In eight patients, a single dose of VOR increased biomarkers of cellular acetylation and induced a mean 4.8-fold increase in HIV RNA expression in resting CD4+ cells. This is the first demonstration that HDAC inhibitors can therapeutically target HIV latency, providing proof-of-concept for this class of drugs as a new therapeutic approach to eradicate HIV infection. The study also highlights the need for further research to optimize dosing regimens and assess the safety and efficacy of HDAC inhibitors in targeting latent proviral genomes.