Evidence map›Paper›PMID 30005017›Full record

Observational studyAIDS (London, England)2018

Variation in cell-associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator brain-and-muscle-ARNT-like-1.

Christina C Chang, Vivek Naranbhai, Jared Stern, Michael Roche, Ashanti Dantanarayana, Ruian Ke, Surekha Tennakoon, Ajantha Solomon, Rebecca Hoh, Wendy Hartogensis and 10 more

Erratum issuedOpen access · greenAbstract readObservational Study
In one paragraph

Observational study in AIDS (London, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.1field-weighted citation impact, top 28% 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

26 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. HIV infection.Nature reviews. Disease primers · 2023
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. The role of latency reversal in HIV cure strategies.Journal of medical primatology · 2022
    Review
  14. Observational
  15. Review
  16. Review
  17. Article
  18. The Circadian Clock and Viral Infections.Journal of biological rhythms · 2021
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 10 institutions in 3 countries.

Christina C ChangDepartment of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia.
Vivek NaranbhaiNuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Jared SternThe Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital.
Michael RocheThe Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital.
Ashanti DantanarayanaThe Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital.
Ruian KeTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
Surekha TennakoonThe Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital.
Ajantha SolomonThe Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital.
Rebecca HohSchool of Medicine.
Wendy HartogensisDivision of Biostatistics.
Frederick M HechtOsher Center for Integrative Medicine, University of California San Francisco, San Francisco, California, USA.
Ken SikarisMelbourne Pathology.
David J PriceThe Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital.
Julian H ElliottDepartment of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia.
Steven G DeeksSchool of Medicine.
Melissa ChurchillSchool of Health and Biomedical Sciences, RMIT University, Melbourne, Australia.
Paul U CameronDepartment of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia.
Nicolas HengartnerTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
Alan S PerelsonTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
Sharon R LewinDepartment of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia.
University of Melbourne · AULos Alamos National Laboratory · USIndiana University School of MedicineMonash University · AUThe Royal Melbourne Hospital · AUCancer Research And Biostatistics · USMelbourne Clinic · AURMIT University · AUUniversity of California, San Francisco · USUniversity of Oxford · GB

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
Viral reservoirs and sanctuaries in HAART - treated patients: role and mechanismsU19AI096109 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DEEKS, STEVEN GRANT, MCCUNE, JOSEPH M · 2011 to 2015
$29.5M
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
Modeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0M
Immune System Modeling/HIVR01AI028433 · NIAID · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 1990 to 2021
$3.7M
NIAID NIH HHS P30 AI027763NIAID NIH HHS R01 AI028433NIAID NIH HHS U19 AI096109NIAID NIH HHS UM1 AI126611NIH HHS R01 OD011095
6 · The paper itself

Abstract

OBJECTIVE(S): To determine whether variation in cell-associated unspliced (CA-US) HIV RNA in HIV-infected individuals on antiretroviral therapy (ART) has a circadian basis.

methodsProspective observational study of HIV-infected individuals on ART. Blood was collected on three occasions and CA-US HIV RNA and mRNA of the circadian-locomotor-output-cycles-kaput (CLOCK)-associated genes quantified by real time PCR. CLOCK-associated proteins were over-expressed in a cell line stably transfected with an HIV long-terminal repeat (LTR) luciferase reporter.

resultsUsing a mixed effects model, there was a significant increase in log-CA-US RNA at the third visit compared with the first visit (effect size of 0.619 with standard error (SE) of 0.098, P < 0.001) and an independent effect of time of blood draw (effect size 0.051 (SE 0.025), P = 0.040). The CLOCK-associated gene, brain-and-muscle-ARNT-like-1 (BMAL-1) had a significant relationship with log CA-US HIV RNA (effect size 8.508 (SE 3.777), P = 0.028) and also with time (P = 0.045). Over expression of BMAL-1 and CLOCK in a cell line stably transfected with an HIV-LTR luciferase reporter resulted in an increase in luciferase expression and this was reduced following mutation of the second E-box in the HIV-LTR.

conclusionThe basal level of HIV transcription on ART can vary significantly and is modulated by the circadian regulator BMAL-1, amongst other factors.

Indexed as

Transcription, GeneticAnti-Retroviral AgentsARNTL Transcription FactorsBlood CellsCells, CulturedFemaleGene Expression ProfilingHIVHIV InfectionsHost-Pathogen InteractionsHumansMaleMiddle AgedReal-Time Polymerase Chain ReactionRNA, ViralAnti-Retroviral AgentsARNTL Transcription FactorsBMAL1 protein, humanRNA, Viral

Identifiers

PMID30005017
PMCPMC6173794
OpenAlexW2884204216

What OpenQuestion holds

Textmetadata
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Read underepoch 390

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.