Evidence map›Paper›PMID 32147687›Full record

ArticleThe Journal of infectious diseases2021

Assessing the Suitability of Next-Generation Viral Outgrowth Assays to Measure Human Immunodeficiency Virus 1 Latent Reservoir Size.

Mars Stone, Daniel I S Rosenbloom, Peter Bacchetti, Xutao Deng, Melanie Dimapasoc, Sheila Keating, Sonia Bakkour, Douglas D Richman, John W Mellors, Steven G Deeks and 8 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

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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 8 institutions in 2 countries.

Mars StoneVitalant Research Institute, San Francisco, California, USA.ORCID 0000-0001-5619-2767
Daniel I S RosenbloomDepartment of Biomedical Informatics, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Peter BacchettiDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Xutao DengVitalant Research Institute, San Francisco, California, USA.
Melanie DimapasocVitalant Research Institute, San Francisco, California, USA.
Sheila KeatingVitalant Research Institute, San Francisco, California, USA.
Sonia BakkourVitalant Research Institute, San Francisco, California, USA.
Douglas D RichmanVA San Diego Healthcare System, San Diego, California, USA.
John W MellorsDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Steven G DeeksDepartment of Medicine, University of California, San Francisco, School of Medicine, San Francisco, California, USA.
Jun LaiDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Subul BegDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Janet D SilicianoDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Amélie PagliuzzaCentre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Nicolas ChomontCentre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Carol Lackman-SmithSouthern Research, Frederick, Maryland, USA.
Roger G PtakSouthern Research, Frederick, Maryland, USA.
Michael P BuschVitalant Research Institute, San Francisco, California, USA.
University of California, San Francisco · USJohns Hopkins University · USCentre Hospitalier de l’Université de Montréal · CASouthern Research Institute · USColumbia University · USPacific Research Institute · USUniversity of California San Diego · USUniversity of Pittsburgh · US

Funding

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
First-in-human study of two anti-SARS CoV-2 antibodies in health volunteersUM1AI126620 · NIAID · WISTAR INSTITUTE · PI MONTANER, LUIS J, RILEY, JAMES L. · 2016 to 2021
$24.5M
Collaboratory of AIDS Researchers for Eradication (CARE)UM1AI126619 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MARGOLIS, DAVID M. · 2016 to 2020
$23.2M
NIAID NIH HHS HHSN272201500017CNIAID NIH HHS UM1 AI126611NIAID NIH HHS UM1 AI126619NIAID NIH HHS UM1 AI126620
6 · The paper itself

Abstract

backgroundEvaluations of human immunodeficiency virus (HIV) curative interventions require reliable and efficient quantification of replication-competent latent reservoirs. The "classic" quantitative viral outgrowth assay (QVOA) has been regarded as the reference standard, although prohibitively resource and labor intensive. We compared 6 "next-generation" viral outgrowth assays, using polymerase chain reaction or ultrasensitive p24 to assess their suitability as scalable proxies for QVOA.

methodsNext-generation QVOAs were compared with classic QVOA using single leukapheresis-derived samples from 5 antiretroviral therapy-suppressed HIV-infected participants and 1 HIV-uninfected control; each laboratory tested blinded batches of 3 frozen and 1 fresh sample. Markov chain Monte Carlo methods estimated extra-Poisson variation at aliquot, batch, and laboratory levels. Models also estimated the effect of testing frozen versus fresh samples.

resultsNext-generation QVOAs had similar estimates of variation to QVOA. Assays with ultrasensitive readout reported higher infectious units per million values than classic QVOA. Within-batch testing had 2.5-fold extra-Poisson variation (95% credible interval [CI], 2.1-3.5-fold) for next-generation assays. Between-laboratory variation increased extra-Poisson variation to 3.4-fold (95% CI, 2.6-5.4-fold). Frozen storage did not substantially alter infectious units per million values (-18%; 95% CI, -52% to 39%).

conclusionsThe data offer cautious support for use of next-generation QVOAs as proxies for more laborious QVOA, while providing greater sensitivities and dynamic ranges. Measurement of latent reservoirs in eradication strategies would benefit from high throughput and scalable assays.

Indexed as

HIV InfectionsVirus LatencyVirus ReplicationAntiretroviral Therapy, Highly ActiveCase-Control StudiesCD4-Positive T-LymphocytesHigh-Throughput Nucleotide SequencingHIV-1HIV Reverse TranscriptaseHumansLeukapheresisViral LoadHIV Reverse Transcriptaseassay comparisonHIV cureHIV reservoirInducible HIV RNAIUPMlatencyleukapheresisquantitative viral out growth assay (QVOA)

Identifiers

PMID32147687
PMCPMC8514180
OpenAlexW3012311927

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.