Evidence map›Paper›PMID 31913161›Full record

ArticleAIDS (London, England)2020

High levels of genetically intact HIV in HLA-DR+ memory T cells indicates their value for reservoir studies.

Bethany A Horsburgh, Eunok Lee, Bonnie Hiener, John-Sebastian Eden, Timothy E Schlub, Susanne von Stockenstrom, Lina Odevall, Jeffrey M Milush, Teri Liegler, Elizabeth Sinclair and 8 more

Open access · hybridAbstract read
In one paragraph

Article in AIDS (London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing 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

37 citing papers in PubMed, 51 citations in OpenAlex.

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  20. Substantial uneven proliferation of CD4Journal of virus eradication · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 4 countries.

Bethany A HorsburghCentre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney.
Eunok LeeCentre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney.
Bonnie HienerCentre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney.
John-Sebastian EdenCentre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney.
Timothy E SchlubSydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Susanne von StockenstromDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Lina OdevallDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Jeffrey M MilushDepartment of Medicine, University of California San Francisco, California.
Teri LieglerDepartment of Medicine, University of California San Francisco, California.
Elizabeth SinclairDepartment of Medicine, University of California San Francisco, California.
Rebecca HohDepartment of Medicine, University of California San Francisco, California.
Eli A BoritzHuman Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Daniel C DouekHuman Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Remi FromentinCentre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Canada.
Nicolas ChomontCentre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Canada.
Steven G DeeksDepartment of Medicine, University of California San Francisco, California.
Frederick M HechtDepartment of Medicine, University of California San Francisco, California.
Sarah PalmerCentre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney.
University of California, San Francisco · USUniversity of Sydney · AUWestmead Institute for Medical Research · AUCentre Hospitalier de l’Université de Montréal · CAKarolinska Institutet · SENational Institute of Allergy and Infectious Diseases · USNational Institutes of Health · US

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MALLORY O JOHNSON · 1988 to 2026
$93.6M
Viral reservoirs and sanctuaries in HAART - treated patients: role and mechanismsU19AI096109 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SCHACKER, TIMOTHY W · 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
NIAID NIH HHS P30 AI027763NIAID NIH HHS U19 AI096109NIAID NIH HHS UM1 AI126611
6 · The paper itself

Abstract

objectiveThe contribution of HLA-DR+ memory CD4 T cells to the HIV reservoir during prolonged antiretroviral therapy is unclear as these cells are commonly excluded when assessing for replication-competent HIV. To address this issue, we examined the distribution of genetically intact HIV DNA within HLA-DR- and HLA-DR+ memory CD4 T cells and the RNA transcriptional profile of these cells during antiretroviral therapy. DESIGN/

methodsFull-length DNA sequencing was used to examine the HIV DNA landscape within HLA-DR+ and HLA-DR- memory CD4 T cells. RNA quantification and sequencing was used to interrogate the relationship between HLA-DR status and HIV RNA transcription.

resultsHLA-DR+ CD4 T cells contained a high frequency of genetically intact HIV genomes, contributing over half of the genetically intact viral sequences to the reservoir. Expansions of genetically identical sequences were identified in all T-cell subsets, indicating that cellular proliferation maintains genetically intact and defective viral DNA during therapy. Intracellular HIV RNA levels in HLA-DR+ and HLA-DR- T cells were not statistically different by either long terminal repeat quantitative PCR quantification or single-genome RNA sequencing of the p6-RT region.

conclusionThe high proportion of intact viral DNA sequences in the proliferative HLA-DR+ subset suggests they are critical in maintaining HIV infection during effective therapy. As such, these cells should be included in any immune intervention targeting HIV during effective therapy.

Indexed as

AdultAnti-HIV AgentsCD4-Positive T-LymphocytesDNA, ViralFemaleHIV-1HIV InfectionsHLA-DR AntigensHumansImmunologic MemoryMaleSequence Analysis, DNASequence Analysis, RNAAnti-HIV AgentsDNA, ViralHLA-DR Antigens

Identifiers

PMID31913161
PMCPMC7071960
OpenAlexW3000050415

What OpenQuestion holds

Textmetadata
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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.