Marie Armani-Tourret, Ce Gao, Ciputra Adijaya Hartana, WeiWei Sun, Leah Carrere, Liliana Vela, Alexander Hochroth, Maxime Bellefroid, Amy Sbrolla, Katrina Shea, Theresa Flynn, Isabelle Roseto, Yelizaveta Rassadkina, Carole Lee, Francoise Giguel, Rajeev Malhotra, Frederic D Bushman, Rajesh T Gandhi, Xu G Yu, Daniel R Kuritzkes, Mathias Lichterfeld
CD4+ T cells with latent HIV-1 infection persist despite treatment with antiretroviral agents and represent the main barrier to a cure of HIV-1 infection. Pharmacological disruption of viral latency may expose HIV-1-infected cells to host immune activity, but the clinical efficacy of latency-reversing agents for reducing HIV-1 persistence remains to be proven. Here, we show in a randomized-controlled human clinical trial that the histone deacetylase inhibitor panobinostat, when administered in combination with pegylated interferon-α2a, induces a structural transformation of the HIV-1 reservoir cell pool, characterized by a disproportionate overrepresentation of HIV-1 proviruses integrated in ZNF genes and in chromatin regions with reduced H3K27ac marks, the molecular target sites for panobinostat...
February 16, 2024: Cell