Evidence map›Paper›PMID 33948574›Full record

ArticleCell reports. Medicine2021

A highly multiplexed droplet digital PCR assay to measure the intact HIV-1 proviral reservoir.

Claire N Levy, Sean M Hughes, Pavitra Roychoudhury, Daniel B Reeves, Chelsea Amstuz, Haiying Zhu, Meei-Li Huang, Yulun Wei, Marta E Bull, Noah A J Cassidy and 12 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports. Medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
9.7field-weighted citation impact, top 1% 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

68 citing papers in PubMed, 102 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Tenofovir, Interferon Pathways, and Mucosal Immunity: Implications for People Living With HIV.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Immortalization and Targeted Enrichment of HIV-Infected CD4International journal of molecular sciences · 2026
    Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 5 institutions in 1 country.

Claire N LevyDepartment of Obstetrics & Gynecology, University of Washington, Seattle, WA, USA.
Sean M HughesDepartment of Obstetrics & Gynecology, University of Washington, Seattle, WA, USA.
Pavitra RoychoudhuryVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Daniel B ReevesVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Chelsea AmstuzVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Haiying ZhuDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Meei-Li HuangDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Yulun WeiDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Marta E BullSeattle Children's Research Institute, Seattle, WA, USA.
Noah A J CassidyHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Jan McClureDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Lisa M FrenkelSeattle Children's Research Institute, Seattle, WA, USA.
Mars StoneVitalent Research Institute, San Francisco, CA, USA.
Sonia BakkourVitalent Research Institute, San Francisco, CA, USA.
Elizabeth R WonderlichDepartment of Infectious Disease Research, Southern Research, 431 Aviation Way, Frederick, MD, USA.
Michael P BuschVitalent Research Institute, San Francisco, CA, USA.
Steven G DeeksSchool of Medicine, University of San Francisco, San Francisco, CA, USA.
Joshua T SchifferVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Robert W CoombsDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Dara A LehmanHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Keith R JeromeVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Florian HladikDepartment of Obstetrics & Gynecology, University of Washington, Seattle, WA, USA.
University of Washington · USFred Hutch Cancer Center · USPacific Research Institute · USSan Francisco General Hospital · USSouthern Research Institute · US

Funding

Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI EDWIN ROBERTO ORELLANA · 1988 to 2026
$104.9M
Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MALLORY O JOHNSON · 1988 to 2026
$93.6M
Social and Behavioral Sciences CoreP30AI064518 · NIAID · DUKE UNIVERSITY · PI GEORGIA Doris TOMARAS · 2005 to 2026
$50.5M
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
Cell and Gene Therapy for HIV CureUM1AI126623 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI JEROME, KEITH R, KIEM, HANS-PETER · 2016 to 2020
$24.2M
VENEREAL DISEASET32AI007140 · NIAID · UNIVERSITY OF WASHINGTON · PI Julia Cook Dombrowski · 1985 to 2026
$19.4M
Infant immune mechanisms of HIV reservoir size and decayR01HD094718 · NICHD · UNIVERSITY OF WASHINGTON · PI JOHN-STEWART, GRACE C., LEHMAN, DARA ANN · 2017 to 2021
$3.6M
Systems and carcinogenic impact assessment of topical microbicides on human mucosaR01AI116292 · NIAID · UNIVERSITY OF WASHINGTON · PI HLADIK, FLORIAN · 2015 to 2019
$3.5M
Role of proviral loci in HIV latencyR01AI125026 · NIAID · UNIVERSITY OF WASHINGTON · PI MULLINS, JAMES IVAN · 2016 to 2019
$3.4M
Extracellular vesicles in semen and genital HIV infection and immunity during heroin addiction and methadone or buprenorphine substitution therapyR01DA040386 · NIDA · UNIVERSITY OF WASHINGTON · PI HLADIK, FLORIAN · 2015 to 2019
$2.6M
Mechanism/predictors of genital/rectal HIV shedding during ART w/plasma <50c/mLR01AI071212 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI FRENKEL, LISA M · 2006 to 2010
$2.4M
NIAID NIH HHS HHSN272201500017CNIAID NIH HHS K25 AI155224NIAID NIH HHS P30 AI027757NIAID NIH HHS P30 AI027763NIAID NIH HHS P30 AI064518NIAID NIH HHS R01 AI071212NIAID NIH HHS R01 AI116292NIAID NIH HHS R01 AI125026NIAID NIH HHS T32 AI007140NIAID NIH HHS UM1 AI106701NIAID NIH HHS UM1 AI126611NIAID NIH HHS UM1 AI126623NICHD NIH HHS R01 HD094718NIDA NIH HHS R01 DA040386
6 · The paper itself

Abstract

Quantifying the replication-competent HIV reservoir is essential for evaluating curative strategies. Viral outgrowth assays (VOAs) underestimate the reservoir because they fail to induce all replication-competent proviruses. Single- or double-region HIV DNA assays overestimate it because they fail to exclude many defective proviruses. We designed two triplex droplet digital PCR assays, each with 2 unique targets and 1 in common, and normalize the results to PCR-based T cell counts. Both HIV assays are specific, sensitive, and reproducible. Together, they estimate the number of proviruses containing all five primer-probe regions. Our 5-target results are on average 12.1-fold higher than and correlate with paired quantitative VOA (Spearman's ρ = 0.48) but estimate a markedly smaller reservoir than previous DNA assays. In patients on antiretroviral therapy, decay rates in blood CD4

Indexed as

Polymerase Chain ReactionDNA, ViralHIV-1HIV InfectionsHIV SeropositivityHumansProvirusesViral LoadVirus LatencyDNA, Viraldigital PCRgenital mucosaHIV cureHIV reservoirintact proviral DNA assayintestinal mucosaIPDAmultiplexingrectalviral outgrowth assay

Identifiers

PMID33948574
PMCPMC8080125
OpenAlexW3152890768

What OpenQuestion holds

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LicenceCC BY
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.