Journal article
Modeling the Effects of Vorinostat In Vivo Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells
R Ke, SR Lewin, JH Elliott, AS Perelson
Plos Pathogens | PUBLIC LIBRARY SCIENCE | Published : 2015
Abstract
Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment. We fitted these models to data collected from a recent clinica..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
This work was performed under the auspices of the U.S. Department of Energy under contract DE-AC52-06NA25396 and supported by NIH grants R01-AI028433, R01-OD011095 and UM1-AI100645 (ASP). SRL is an NHMRC Practitioner Fellow. This work was also supported by NHMRC project grants # 4911954 and # 1002671 and the National Institutes of Health Delaney AIDS Research Enterprise (DARE) to find a cure U19 AI096109. The clinical study of vorinostat was supported in part by a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp. 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.