Evidence map›Paper›PMID 26478893›Full record

ReviewOpen forum infectious diseases2015

Designing and Interpreting Limiting Dilution Assays: General Principles and Applications to the Latent Reservoir for Human Immunodeficiency Virus-1.

Daniel I S Rosenbloom, Oliver Elliott, Alison L Hill, Timothy J Henrich, Janet M Siliciano, Robert F Siliciano

Registry-linked trialOpen access · goldAbstract readReview
In one paragraph

Review in Open forum infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04938518 (Investigation of the Impact of Inducible, Replication-competent Latent HIV-1 as an Impediment to HIV/AIDS Cure in the Context of Sustained Viral Suppression), which is not on this map. Cited by 105 papers.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed
7.6field-weighted citation impact, top 2% 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.

NCT04938518 unknown statusnot on this mapstarted 2019, after this paper: background citation

Investigation of the Impact of Inducible, Replication-competent Latent HIV-1 as an Impediment to HIV/AIDS Cure in the Context of Sustained Viral Suppression

Typeobservational_patient_registrySponsorKenya Medical Research InstituteRan2019 to 2022Enrolled222ConditionsHIV-1-infection
3 · Its place in the literature

Who cites it

105 citing papers in PubMed, 129 citations in OpenAlex.

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

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

6 authors at 5 institutions in 1 country.

Daniel I S RosenbloomDepartment of Biomedical Informatics , Columbia University Medical Center , New York, New York.
Oliver ElliottDepartment of Biomedical Informatics , Columbia University Medical Center , New York, New York.
Alison L HillProgram for Evolutionary Dynamics , Harvard University , Cambridge.
Timothy J HenrichDivision of Infectious Diseases , Brigham and Women's Hospital , Boston, Massachusetts.
Janet M SilicianoDepartment of Medicine , Johns Hopkins University School of Medicine.
Robert F SilicianoDepartment of Medicine , Johns Hopkins University School of Medicine ; Howard Hughes Medical Institute , Baltimore, Maryland.
Columbia University Irving Medical Center · USBrigham and Women's Hospital · USHarvard University · USJohns Hopkins Medicine · USJohns Hopkins University · US

Funding

Vaccine Response and Immunotherapeutics SWGP30AI094189 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Richard E. Chaisson · 2012 to 2026
$67.0M
Training in Biomedical Informatics at Columbia UniversityT15LM007079 · NLM · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI NOEMIE ELHADAD, GEORGE M HRIPCSAK · 1992 to 2026
$28.9M
Quantification and prediction of treatment efficacy for HIV cure strategiesDP5OD019851 · OD · JOHNS HOPKINS UNIVERSITY · PI HILL, ALISON LYNN · 2014 to 2018
$2.1M
Uncovering Evolutionary History using the Topology of Genomic Data with Applications to HIVR01GM117591 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI RABADAN, RAUL · 2015 to 2018
$1.3M
Impact of Chemotherapy and Stem Cell Transplant on HIV-1 Reservoir DynamicsK23AI098480 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HENRICH, TIMOTHY JENSEN · 2012 to 2016
$673k
NIAID NIH HHS K23 AI098480NIAID NIH HHS P30 AI094189NIGMS NIH HHS R01 GM117591NIH HHS DP5 OD019851NLM NIH HHS T15 LM007079
6 · The paper itself

Abstract

Limiting dilution assays are widely used in infectious disease research. These assays are crucial for current human immunodeficiency virus (HIV)-1 cure research in particular. In this study, we offer new tools to help investigators design and analyze dilution assays based on their specific research needs. Limiting dilution assays are commonly used to measure the extent of infection, and in the context of HIV they represent an essential tool for studying latency and potential curative strategies. Yet standard assay designs may not discern whether an intervention reduces an already miniscule latent infection. This review addresses challenges arising in this setting and in the general use of dilution assays. We illustrate the major statistical method for estimating frequency of infectious units from assay results, and we offer an online tool for computing this estimate. We recommend a procedure for customizing assay design to achieve desired sensitivity and precision goals, subject to experimental constraints. We consider experiments in which no viral outgrowth is observed and explain how using alternatives to viral outgrowth may make measurement of HIV latency more efficient. Finally, we discuss how biological complications, such as probabilistic growth of small infections, alter interpretations of experimental results.

Indexed as

dilution assayHIVlatent reservoirmaximum-likelihood statisticsviral outgrowth

Identifiers

PMID26478893
PMCPMC4602119
OpenAlexW1771860521

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.