Evidence map›Paper›PMID 33420062›Full record

ArticleNature communications2021

HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA).

Natalie N Kinloch, Yanqin Ren, Winiffer D Conce Alberto, Winnie Dong, Pragya Khadka, Szu Han Huang, Talia M Mota, Andrew Wilson, Aniqa Shahid, Don Kirkby and 15 more

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2021. 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 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
–field-weighted citation impact
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

74 citing papers in PubMed.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Natalie N Kinloch *Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
Yanqin Ren *Infectious Diseases Division, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Winiffer D Conce AlbertoInfectious Diseases Division, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Winnie DongBritish Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
Pragya KhadkaInfectious Diseases Division, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Szu Han HuangInfectious Diseases Division, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Talia M MotaInfectious Diseases Division, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Andrew WilsonDepartment of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC, USA.
Aniqa ShahidFaculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
Don KirkbyBritish Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
Marianne HarrisBritish Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
Colin KovacsMaple Leaf Medical Clinic, Toronto, ON, Canada.
Erika BenkoMaple Leaf Medical Clinic, Toronto, ON, Canada.
Mario A OstrowskiDepartment of Medicine, University of Toronto, Toronto, ON, Canada.
Perla M Del Rio EstradaCenter for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico.
Avery WimpelbergWhitman Walker Health, Washington, DC, USA.
Christopher CannonWhitman Walker Health, Washington, DC, USA.
W David HardyWhitman Walker Health, Washington, DC, USA.
Lynsay MacLarenWhitman Walker Health, Washington, DC, USA.
Harris GoldsteinDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0003-0543-6025
Chanson J BrummeBritish Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
Guinevere Q LeeInfectious Diseases Division, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Rebecca M LynchDepartment of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC, USA.
Zabrina L BrummeFaculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada. zbrumme@sfu.ca.ORCID http://orcid.org/0000-0002-8157-1037
R Brad JonesInfectious Diseases Division, Department of Medicine, Weill Cornell Medical College, New York, NY, USA. rbjones@med.cornell.edu.ORCID http://orcid.org/0000-0003-4470-1231

Funding

BELIEVE: Bench to Bed Enhanced Lymphocyte Infusions to Engineer Viral EradicationUM1AI126617 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI JONES, R. BRAD, NIXON, DOUGLAS F · 2016 to 2020
$28.1M
Targeted delivery of cytopathicity enhancing agents, and co-ordination with shock and kill, to reduce HIV reservoirsR01AI147845 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI IRVINE, DARRELL J, JONES, R. BRAD · 2019 to 2023
$4.0M
CTL-Mediated Elimination of Replication Competent vs. Defective HIV Proviruses from Natural Latent Reservoirs: Roles of Antigen Specificity and Functional CharacteristicsR01AI131798 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI JONES, R. BRAD · 2017 to 2021
$2.1M
Acquisition of the BioRad QX200 AutoDG Droplet Digital PCR SystemS10OD021622 · OD · GEORGE WASHINGTON UNIVERSITY · PI JONES, R. BRAD · 2016 to 2016
$125k
CIHR HB1-164063CIHR PJT-159625NIAID NIH HHS R01 AI131798NIAID NIH HHS R01 AI147845NIAID NIH HHS UM1 AI126617NIH HHS S10 OD021622
6 · The paper itself

Abstract

The Intact Proviral DNA Assay (IPDA) was developed to address the critical need for a scalable method for intact HIV-1 reservoir quantification. This droplet digital PCR-based assay simultaneously targets two HIV-1 regions to distinguish genomically intact proviruses against a large background of defective ones, and its application has yielded insights into HIV-1 persistence. Reports of assay failures however, attributed to HIV-1 polymorphism, have recently emerged. Here, we describe a diverse North American cohort of people with HIV-1 subtype B, where the IPDA yielded a failure rate of 28% due to viral polymorphism. We further demonstrate that within-host HIV-1 diversity can lead the IPDA to underestimate intact reservoir size, and provide examples of how this phenomenon could lead to erroneous interpretation of clinical trial data. While the IPDA represents a major methodological advance, HIV-1 diversity should be addressed before its widespread adoption as a principal readout in HIV-1 remission trials.

Indexed as

BiodiversityBase SequenceCD4-Positive T-LymphocytesDNA, ViralHIV-1HIV InfectionsHumansPhylogenyPolymerase Chain ReactionProvirusesDNA, Viral

Identifiers

PMID33420062
PMCPMC7794580

What OpenQuestion holds

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Registered trials

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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.