Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing

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Combination antiretroviral therapy has greatly improved the clinical outcome of HIV infection treatment. However, latent viral reservoirs established primarily in memory CD4 T cells persist even after long periods of suppressive antiretroviral therapy, which hinders the ability to achieve a prolonged drug-free remission or a cure of the HIV infection. Activation of HIV expression from latent reservoirs is a part of proposed strategies that may potentially lead to virus elimination and ultimately cure of the infection. In this study, we show that romidepsin, a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, is a potent activator of HIV expression in an in vitro model of viral latency as well as ex vivo in resting and memory CD4 T cells isolated from HIV-infected patients with suppressed viremia. Importantly, the ex vivo activation of latent HIV occurred at romidepsin concentrations lower than those achieved in drug-treated lymphoma patients. In addition, romidepsin exhibited a more potent effect than other drugs in the same class that have already been shown to activate HIV expression in vivo. Together, these results support the clinical assessment of romidepsin in HIV-infected patients on suppressive antiretroviral therapy.

Vyšlo v časopise: Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004071
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004071

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