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Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.

Publication ,  Journal Article
Archin, NM; Liberty, AL; Kashuba, AD; Choudhary, SK; Kuruc, JD; Crooks, AM; Parker, DC; Anderson, EM; Kearney, MF; Strain, MC; Richman, DD ...
Published in: Nature
July 25, 2012

Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

July 25, 2012

Volume

487

Issue

7408

Start / End Page

482 / 485

Location

England

Related Subject Headings

  • Vorinostat
  • Virus Latency
  • Viremia
  • Up-Regulation
  • Risk Assessment
  • RNA, Viral
  • Proviruses
  • Hydroxamic Acids
  • Humans
  • Histones
 

Citation

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Chicago
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MLA
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Archin, N. M., Liberty, A. L., Kashuba, A. D., Choudhary, S. K., Kuruc, J. D., Crooks, A. M., … Margolis, D. M. (2012). Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature, 487(7408), 482–485. https://doi.org/10.1038/nature11286
Archin, N. M., A. L. Liberty, A. D. Kashuba, S. K. Choudhary, J. D. Kuruc, A. M. Crooks, D. C. Parker, et al. “Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.Nature 487, no. 7408 (July 25, 2012): 482–85. https://doi.org/10.1038/nature11286.
Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature. 2012 Jul 25;487(7408):482–5.
Archin, N. M., et al. “Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.Nature, vol. 487, no. 7408, July 2012, pp. 482–85. Pubmed, doi:10.1038/nature11286.
Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, Parker DC, Anderson EM, Kearney MF, Strain MC, Richman DD, Hudgens MG, Bosch RJ, Coffin JM, Eron JJ, Hazuda DJ, Margolis DM. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature. 2012 Jul 25;487(7408):482–485.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

July 25, 2012

Volume

487

Issue

7408

Start / End Page

482 / 485

Location

England

Related Subject Headings

  • Vorinostat
  • Virus Latency
  • Viremia
  • Up-Regulation
  • Risk Assessment
  • RNA, Viral
  • Proviruses
  • Hydroxamic Acids
  • Humans
  • Histones