Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy

Journal article

Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy

PLoS pathogens | Published : 2014

Abstract

UNLABELLED: Human immunodeficiency virus (HIV) persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs) are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi) may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART). The primary endpoint was change in cell associated unspliced (CA-US) HIV RNA in total CD4+ T-cells from blood at day 14. ..

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University of Melbourne Researchers

Miranda Smith Author

Ricky Johnstone Author

Timothy Spelman Author

Henry Prince Author

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IMPROVED HEALTH OUTCOMES FOR PEOPLE LIVING WITH HIV

Despite the success of antiviral therapy for HIV infection, HIV cannot be cured and treatment is life long. In addition, there are complicat..

Grants

Awarded by Merck

Funding Acknowledgements

The study was supported in part by a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp. This work was supported in part by the Australian National Health and Medical Research Council (APP1042654, Dora Lush Postgraduate Scholarship APP607230, CJ Martin Overseas Biomedical Fellowship GNT0490988, Early Career Fellowship APP1037839) and the Division of AIDS, National Institute of Allergy and Infectious Disease, US National Institutes of Health (DARE: Delaney AIDS Research Enterprise; U19AI096109). RF is supported by the American Foundation for AIDS Research (108264). SRL is a NHMRC Practitioner Fellow and RWJ is an NHMRC Principal Research Fellow. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.