A highly multiplexed droplet digital PCR assay to measure the intact HIV-1 proviral reservoir Article Swipe
Claire 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
,
Jan McClure
,
Lisa M. Frenkel
,
Mars Stone
,
Sonia Bakkour
,
Elizabeth R. Wonderlich
,
Michael P. Busch
,
Steven G. Deeks
,
Joshua T. Schiffer
,
Robert W. Coombs
,
Dara A. Lehman
,
Keith R. Jerome
,
Florian Hladik
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1016/j.xcrm.2021.100243
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1016/j.xcrm.2021.100243
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+ T cells are faster for intact than for defective proviruses, and intact provirus frequencies are similar in mucosal and circulating T cells.
Related Topics
Concepts
Digital polymerase chain reaction
Human immunodeficiency virus (HIV)
Measure (data warehouse)
Virology
Biology
Computational biology
Polymerase chain reaction
Computer science
Gene
Biochemistry
Database
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.xcrm.2021.100243
- http://www.cell.com/article/S2666379121000598/pdf
- OA Status
- gold
- Cited By
- 93
- References
- 83
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3152890768
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3152890768Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1016/j.xcrm.2021.100243Digital Object Identifier
- Title
-
A highly multiplexed droplet digital PCR assay to measure the intact HIV-1 proviral reservoirWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-04-01Full publication date if available
- Authors
-
Claire 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, Jan McClure, Lisa M. Frenkel, Mars Stone, Sonia Bakkour, Elizabeth R. Wonderlich, Michael P. Busch, Steven G. Deeks, Joshua T. Schiffer, Robert W. Coombs, Dara A. Lehman, Keith R. Jerome, Florian HladikList of authors in order
- Landing page
-
https://doi.org/10.1016/j.xcrm.2021.100243Publisher landing page
- PDF URL
-
https://www.cell.com/article/S2666379121000598/pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.cell.com/article/S2666379121000598/pdfDirect OA link when available
- Concepts
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Digital polymerase chain reaction, Human immunodeficiency virus (HIV), Measure (data warehouse), Virology, Biology, Computational biology, Polymerase chain reaction, Computer science, Gene, Biochemistry, DatabaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
93Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 26, 2024: 16, 2023: 26, 2022: 17, 2021: 8Per-year citation counts (last 5 years)
- References (count)
-
83Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.therapy, | 121 |
| abstract_inverted_index.12.1-fold | 94 |
| abstract_inverted_index.PCR-based | 64 |
| abstract_inverted_index.Together, | 76 |
| abstract_inverted_index.correlate | 98 |
| abstract_inverted_index.defective | 40, 135 |
| abstract_inverted_index.essential | 6 |
| abstract_inverted_index.normalize | 60 |
| abstract_inverted_index.outgrowth | 12 |
| abstract_inverted_index.reservoir | 4, 17, 112 |
| abstract_inverted_index.specific, | 72 |
| abstract_inverted_index.containing | 83 |
| abstract_inverted_index.evaluating | 8 |
| abstract_inverted_index.proviruses | 82 |
| abstract_inverted_index.sensitive, | 73 |
| abstract_inverted_index.(Spearman's | 103 |
| abstract_inverted_index.Quantifying | 0 |
| abstract_inverted_index.circulating | 146 |
| abstract_inverted_index.frequencies | 140 |
| abstract_inverted_index.proviruses, | 136 |
| abstract_inverted_index.proviruses. | 25, 41 |
| abstract_inverted_index.strategies. | 10 |
| abstract_inverted_index.overestimate | 32 |
| abstract_inverted_index.primer-probe | 86 |
| abstract_inverted_index.quantitative | 101 |
| abstract_inverted_index.double-region | 28 |
| abstract_inverted_index.reproducible. | 75 |
| abstract_inverted_index.underestimate | 15 |
| abstract_inverted_index.antiretroviral | 120 |
| abstract_inverted_index.CD4<sup>+</sup> | 126 |
| abstract_inverted_index.replication-competent | 2, 24 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 98 |
| corresponding_author_ids | https://openalex.org/A5060698792, https://openalex.org/A5014597522 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 22 |
| corresponding_institution_ids | https://openalex.org/I201448701, https://openalex.org/I4210089486 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8100000023841858 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.99100877 |
| citation_normalized_percentile.is_in_top_1_percent | True |
| citation_normalized_percentile.is_in_top_10_percent | True |