Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy
- PMID: 22837004
- PMCID: PMC3704185
- DOI: 10.1038/nature11286
Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy
Erratum in
- Nature. 2012 Sep 20;489(7416):460
Abstract
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.
Trial registration: ClinicalTrials.gov NCT01319383.
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Comment in
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HIV: Shock and kill.Nature. 2012 Jul 25;487(7408):439-40. doi: 10.1038/487439a. Nature. 2012. PMID: 22836995 No abstract available.
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Viral infection: Coaxing HIV out of hiding.Nat Rev Microbiol. 2012 Sep;10(9):596-7. doi: 10.1038/nrmicro2861. Epub 2012 Aug 13. Nat Rev Microbiol. 2012. PMID: 22886238 No abstract available.
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References
-
- Blankson JN, Persaud D, Siliciano RF. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med. 2002;53:557. - PubMed
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