Evidence map›Paper›PMID 33647768›Full record

ArticleEBioMedicine2021

Multiply spliced HIV RNA is a predictive measure of virus production ex vivo and in vivo following reversal of HIV latency.

Jennifer M Zerbato, Georges Khoury, Wei Zhao, Matthew J Gartner, Rachel D Pascoe, Ajantha Rhodes, Ashanti Dantanarayana, Megan Gooey, Jenny Anderson, Peter Bacchetti and 6 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
4.4field-weighted citation impact, top 5% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 47 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 2 countries.

Jennifer M ZerbatoDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Georges KhouryDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Wei ZhaoDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Matthew J GartnerSchool of Health and Biomedical Sciences, RMIT University, Melbourne, Australia.
Rachel D PascoeDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Ajantha RhodesDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Ashanti DantanarayanaDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Megan GooeyHIV Characterisation Laboratory, Victorian Infectious Diseases Reference Laboratory, the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Jenny AndersonDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Peter BacchettiDepartment of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
Steven G DeeksDepartment of Medicine, Division of HIV/AIDS, University of California San Francisco, San Francisco, USA.
James McMahonDepartment of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia.
Michael RocheDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia.
Thomas A RasmussenDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Damian Fj PurcellDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Sharon R LewinDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. Electronic address: sharon.lewin@unimelb.edu.au.
The University of Melbourne · AUUniversity of California, San Francisco · USMonash University · AURMIT University · AUThe Royal Melbourne Hospital · AUVictorian Infectious Diseases Reference Laboratory · AU

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
Delaney AIDS Research Enterprise to Cure HIVUM1AI126611 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DEEKS, STEVEN GRANT, PICKER, LOUIS J. · 2016 to 2020
$27.9M
NIAID NIH HHS P30 AI027763NIAID NIH HHS UM1 AI126611
6 · The paper itself

Abstract

backgroundOne strategy being pursued to clear latently infected cells that persist in people living with HIV (PLWH) on antiretroviral therapy (ART) is to activate latent HIV infection with a latency reversing agent (LRA). Surrogate markers that accurately measure virus production following an LRA are needed.

methodsWe quantified cell-associated unspliced (US), multiply spliced (MS) and supernatant (SN) HIV RNA by qPCR from total and resting CD4+ T cells isolated from seven PLWH on ART before and after treatment ex vivo with different LRAs, including histone deacetylase inhibitors (HDACi). MS and plasma HIV RNA were also quantified from PLWH on ART (n-11) who received the HDACi panobinostat.

findingsIn total and resting CD4+ T cells from PLWH on ART, detection of US RNA was common while detection of MS RNA was infrequent. Primers used to detect MS RNA, in contrast to US RNA, bound sites of the viral genome that are commonly mutated or deleted in PLWH on ART. Following ex vivo stimulation with LRAs, we identified a strong correlation between the fold change increase in SN and MS RNA, but not the fold change increase in SN and US RNA. In PLWH on ART who received panobinostat, MS RNA was significantly higher in samples with detectable compared to non0detectable plasma HIV RNA.

interpretationFollowing administration of an LRA, quantification of MS RNA is more likely to reflect an increase in virion production and is therefore a better indicator of meaningful latency reversal.

fundingNHMRC, NIH DARE collaboratory.

Indexed as

RNA SplicingAnti-Retroviral AgentsCD4-Positive T-LymphocytesCell ProliferationHistone Deacetylase InhibitorsHIV-1HIV InfectionsHumansPolyhydroxyalkanoatesRNA, ViralTetradecanoylphorbol AcetateVirus LatencyVorinostatAnti-Retroviral AgentsHistone Deacetylase InhibitorsPolyhydroxyalkanoatesRNA, ViralTetradecanoylphorbol AcetateVorinostatBiomarkerHIVLatency reversalMultiply-spliced HIV RNAReservoirShock and kill

Identifiers

PMID33647768
PMCPMC7920823
OpenAlexW3134500249

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.