Molecular Medicine

, Volume 17, Issue 5–6, pp 466–472 | Cite as

Histone Deacetylase Inhibitors for Purging HIV-1 from the Latent Reservoir

  • Shay Matalon
  • Thomas A Rasmussen
  • Charles A Dinarello
Review Article


A reservoir of latently infected memory CD4+T cells is believed to be the source of HIV-1 reemergence after discontinuation of antiretroviral therapy. HIV-1 eradication may depend on depletion of this reservoir. Integrated HIV-1 is inaccessible for expression, in part because of histone deacetylases (HDACs). One approach is to exploit the ability of HDAC inhibitors to induce HIV-1 expression from an integrated virus. With effective antiretroviral therapy, newly expressed HIV-1 is incapable of reinfecting naive cells. With HIV-1 expression, one assumes the infected cell dies and there is a progressive reduction in the size of the reservoir. The concept was tested using the HDAC inhibitor valproic acid. However, valproic acid is weak in inducing HIV-1 from latency in vitro. As such, clinical trials revealed a small or no effect on reducing the number of latently infected T cells in the peripheral blood. However, the new HDAC inhibitors vorinostat, belinostat and givinostat are more effective at targeting specific HDACs for HIV-1 expression than valproic acid. Here, we review studies on HDAC inhibitor-induced expression of latent HIV-1, with an emphasis on new and specific HDAC inhibitors. With increased potency for HIV-1 expression as well as safety and ease of oral administration, new HDAC inhibitors offer a unique opportunity to deplete the latent reservoir. An additional benefit is the antiinflammatory properties of HDAC inhibitors, including downregulation of HIV-1 coreceptor expression.



The authors thank Gregory Pott, Carrie Sailer, Leland Shapiro and Marcel F. Nold for their contributions. This work was supported by National Institutes of Health Grant AI-15614 (to CAD) and Ital-farmaco, SpA, Cinisello Balsamo, Italy.


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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Shay Matalon
    • 1
  • Thomas A Rasmussen
    • 2
  • Charles A Dinarello
    • 1
  1. 1.Department of Medicine, Division of Infectious DiseasesUniversity of Colorado DenverAuroraUSA
  2. 2.Department of Infectious DiseasesAarhus University HospitalSkejbyDenmark

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