Evidence map›Paper›PMID 22837004›Full record

ArticleNature2012

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

N M Archin, A L Liberty, A D Kashuba, S K Choudhary, J D Kuruc, A M Crooks, D C Parker, E M Anderson, M F Kearney, M C Strain and 7 more

Erratum issued 7 registry-linked trialsAbstract read
In one paragraph

Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 7 registered trials, which are not on this map. Cited by 813 papers.

0numbers the graph read from it
0cells of the map it votes in
813citing papers in PubMed
47.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01319383 phase1 / phase2completednot on this map

A Phase I/II Investigation of the Effect of Vorinostat (VOR) on HIV RNA Expression in the Resting CD4+ T Cells of HIV-Infected Patients Receiving Stable Antiretroviral Therapy

TypeinterventionalSponsorUniversity of North Carolina, Chapel HillRan2011 to 2016Enrolled25ConditionsHIV-1 InfectionArmsVorinostat
NCT02042248 phase1completednot on this mapstarted 2014, after this paper: background citation

IGHID 1309 -A Phase I Study to Evaluate the Kinetics of the Immunologic Response and Virologic Impact of AGS-004 in HIV-Infected Individuals Suppressed on Antiretroviral Therapy Initiated During Acute and Chronic HIV Infection

TypeinterventionalSponsorCynthia L Gay, MDRan2014 to 2016Enrolled6ConditionsHIVArmsAGS-004
NCT02071095 phase1 / phase2completednot on this mapstarted 2014, after this paper: background citation

Simultaneous Disruption of Latency and Immune Enhancement by Poly-ICLC During HIV-1 Infection

TypeinterventionalSponsorNina BhardwajRan2014 to 2016Enrolled15ConditionsHIV-1 Infected Adults With Chronic HIV-1 InfectionArmsArm A: Poly-ICLC, Arm B: Normal Saline
NCT02208167 phase1completednot on this mapstarted 2015, after this paper: background citation

IGHID 1320 - A Phase I Study to Evaluate the Safety, Immunologic, and Virologic Responses of HIV-1 Antigen Expanded Specific T Cell Therapy (HXTC) as a Therapeutic Strategy in HIV-Infected Individuals Started on Antiretroviral Therapy During Acute and Chronic Infection

TypeinterventionalSponsorUniversity of North Carolina, Chapel HillRan2015 to 2017Enrolled6ConditionsHIVArmsHXTC infusion
NCT02336074 phase2completednot on this mapstarted 2015, after this paper: background citation

Research In Viral Eradication of HIV Reservoirs

TypeinterventionalSponsorImperial College LondonRan2015 to 2023Enrolled60ConditionsHIVArmsCombination Antiretroviral Therapy (cART), Raltegravir, Vorinostat, ChAdV63.HIVconsv (ChAd), MVA.HIVconsv (MVA)
NCT02475915 phase1 / phase2completednot on this mapstarted 2015, after this paper: background citation

A Randomized Study to Compare the Efficacy of Vorinostat/Hydroxychloroquine/Maraviroc (VHM) in Controlling HIV After Treatment Interruption in Subjects Who Initiated ART During Acute HIV Infection

TypeinterventionalSponsorSEARCH Research FoundationRan2015 to 2016Enrolled15ConditionsAcute HIV InfectionArmsVorinostat, Hydroxychloroquine, Maraviroc, Tenofovir, Emtricitabine
NCT02707900 phase1terminatednot on this mapstarted 2016, after this paper: background citation

IGHID 11424 - A Pilot Trial of the Effect of Vorinostat and AGS-004 on Persistent HIV-1 Infection (The VOR VAX Study)

TypeinterventionalSponsorUniversity of North Carolina, Chapel HillRan2016 to 2018Enrolled6ConditionsHIV-1 InfectionArmsVorinostat, AGS-004
3 · Its place in the literature

Who cites it

813 citing papers in PubMed, 1,152 citations in OpenAlex.

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753 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

N M ArchinThe University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
A L Liberty
A D Kashuba
S K Choudhary
J D Kuruc
A M Crooks
D C Parker
E M Anderson
M F Kearney
M C Strain
D D Richman
M G Hudgens
R J Bosch
J M Coffin
J J Eron
D J Hazuda
D M Margolis
University of North Carolina at Chapel Hill · USVA San Diego Healthcare System · USHarvard University · USMerck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
UNC CLINICAL AND TRANSLATIONAL SCIENCE AWARD: BPCAUL1RR025747 · NCRR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUNGE, MARSCHALL S. · 2008 to 2011
$44.6M
Using NK Cells to eliminate the latent HIV reservoirU19AI096113 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI OTT, MELANIE MARIA · 2011 to 2015
$39.5M
A Phase II/II Investigation of the Effect of Vorinostat (VOR) in HIV InfectionU01AI095052 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MARGOLIS, DAVID M. · 2011 to 2013
$1.7M
The in vivo effect of HDAC Inhibitors on HIV gene expression in resting CD4+ T CeR34AI084553 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MARGOLIS, DAVID M. · 2009 to 2009
$111k
NCRR NIH HHS RR024383NCRR NIH HHS UL1 RR025747NIAID NIH HHS AI084553NIAID NIH HHS AI095052NIAID NIH HHS AI096113NIAID NIH HHS AI50410NIAID NIH HHS P30 AI050410NIAID NIH HHS R34 AI084553NIAID NIH HHS U01 AI095052NIAID NIH HHS U19 AI096113
6 · The paper itself

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.

Indexed as

AcetylationAnti-HIV AgentsBiomarkersCD4-Positive T-LymphocytesGene Expression Regulation, ViralHistone Deacetylase InhibitorsHistonesHIV-1HIV InfectionsHumansHydroxamic AcidsProvirusesRisk AssessmentRNA, ViralUp-RegulationViremiaAnti-HIV AgentsBiomarkersHistone Deacetylase InhibitorsHistonesHydroxamic AcidsRNA, ViralVorinostat

Identifiers

PMID22837004
PMCPMC3704185
OpenAlexW2055796578

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

and 1 more above

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.