A study published in *Nature* (487(7408): 482–485. doi:10.1038/nature11286) demonstrates that vorinostat (VOR), a histone deacetylase (HDAC) inhibitor, can disrupt HIV-1 latency in patients on antiretroviral therapy (ART). Despite ART, HIV-1 remains latent in resting CD4+ T cells, posing a major obstacle to cure. VOR, which inhibits HDACs, was shown to increase HIV RNA expression in these cells, indicating that it can target the molecular mechanisms maintaining latency. The study involved eight patients with undetectable plasma HIV RNA, and VOR increased HIV RNA expression by 4.8-fold in resting CD4+ T cells. This is the first evidence that HDAC inhibitors can directly target HIV latency in humans, providing proof of concept for their use in treating HIV. The study also evaluated the pharmacokinetics of VOR, showing that it reached therapeutic concentrations in plasma. VOR increased histone acetylation, a key factor in HIV latency, and induced HIV RNA expression in resting CD4+ T cells. The results suggest that VOR can disrupt the latency of HIV in patients on ART, potentially leading to the eradication of the virus. However, the study also notes that while VOR increases HIV RNA expression, it does not significantly reduce low-level viremia, possibly due to the low baseline levels of viremia in the patients studied. The study highlights the potential of HDAC inhibitors as a new class of therapeutic agents for HIV. It also underscores the need for further research to determine the optimal dosing regimens and to explore the long-term effects of VOR on HIV latency. The findings support the feasibility of targeting persistent, latent HIV infection within resting CD4+ T cells, opening the way for the development of more specific and effective HDAC inhibitors for HIV treatment.A study published in *Nature* (487(7408): 482–485. doi:10.1038/nature11286) demonstrates that vorinostat (VOR), a histone deacetylase (HDAC) inhibitor, can disrupt HIV-1 latency in patients on antiretroviral therapy (ART). Despite ART, HIV-1 remains latent in resting CD4+ T cells, posing a major obstacle to cure. VOR, which inhibits HDACs, was shown to increase HIV RNA expression in these cells, indicating that it can target the molecular mechanisms maintaining latency. The study involved eight patients with undetectable plasma HIV RNA, and VOR increased HIV RNA expression by 4.8-fold in resting CD4+ T cells. This is the first evidence that HDAC inhibitors can directly target HIV latency in humans, providing proof of concept for their use in treating HIV. The study also evaluated the pharmacokinetics of VOR, showing that it reached therapeutic concentrations in plasma. VOR increased histone acetylation, a key factor in HIV latency, and induced HIV RNA expression in resting CD4+ T cells. The results suggest that VOR can disrupt the latency of HIV in patients on ART, potentially leading to the eradication of the virus. However, the study also notes that while VOR increases HIV RNA expression, it does not significantly reduce low-level viremia, possibly due to the low baseline levels of viremia in the patients studied. The study highlights the potential of HDAC inhibitors as a new class of therapeutic agents for HIV. It also underscores the need for further research to determine the optimal dosing regimens and to explore the long-term effects of VOR on HIV latency. The findings support the feasibility of targeting persistent, latent HIV infection within resting CD4+ T cells, opening the way for the development of more specific and effective HDAC inhibitors for HIV treatment.