Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy

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The major barrier to curing HIV is the long term persistence of latently infected resting memory T-cells in HIV-infected patients on antiretroviral therapy (ART). One strategy being pursued to eliminate latently infected cells is to activate HIV production from latently infected cells with the aim of killing latently infected cells via virus induced cell death or stimulation of an HIV-specific immune response. Histone deacetylases (HDACs) are important in maintaining HIV latency. Vorinostat, an inhibitor of HDACs (HDACi) licensed for the treatment of some malignancies, has been shown in laboratory studies and a clinical study of selected individuals to disrupt HIV latency. We examined the ability of standard dose vorinostat given daily for 14 days to activate latent HIV infection in unselected HIV-infected individuals on ART. The study showed evidence of activation of latent HIV infection in 18/20 (90%) of individuals and was safe and generally well tolerated. There were significant early changes in host gene expression, which persisted during and after the period of vorinostat. No changes were seen in immune activation or number of latently infected cells. Vorinostat was able to activate latent HIV infection in most individuals. Additional interventions will be needed to eliminate latent HIV infection.

Vyšlo v časopise: Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy. PLoS Pathog 10(11): e32767. doi:10.1371/journal.ppat.1004473
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004473

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