Evidence map›Paper›PMID 30964884›Full record

Observational studyPloS one2019

Validation of publicly-available software used in analyzing NGS data for HIV-1 drug resistance mutations and transmission networks in a Washington, DC, Cohort.

Kamwing Jair, Chase D McCann, Harrison Reed, Amanda D Castel, Marcos Pérez-Losada, Brittany Wilbourn, Alan E Greenberg, Jeanne A Jordan, DC Cohort Executive Committee

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

8 citing papers in PubMed, 10 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

9 authors at 2 institutions in 2 countries.

Kamwing JairDepartment of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States of America.
Chase D McCannDepartment of Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, NY, United States of America.
Harrison ReedDepartment of Forensic Sciences, Public Health Laboratory, District of Columbia, Washington, DC, United States of America.
Amanda D CastelDepartment of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States of America.
Marcos Pérez-LosadaDepartment of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States of America.
Brittany WilbournDepartment of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States of America.
Alan E GreenbergDepartment of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States of America.
Jeanne A JordanDepartment of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States of America.ORCID 0000-0002-1859-1393
DC Cohort Executive Committee
Milken Institute · USCornell University · US

Funding

CPCRA Clinical Trials UnitU01AI069503 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI GORDIN, FRED M · 2007 to 2011
$33.9M
SWG 2: Cure Research Scientific Working GroupP30AI117970 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI Italo Mocchetti · 2015 to 2026
$29.6M
NIAID NIH HHS P30 AI117970NIAID NIH HHS U01 AI069503
6 · The paper itself

Abstract

The DC Cohort is an ongoing longitudinal observational study of persons living with HIV. To better understand HIV-1 drug resistance and potential transmission clusters among these participants, we performed targeted, paired-end next-generation sequencing (NGS) of protease, reverse transcriptase and integrase amplicons. We elected to use free, publicly-available software (HyDRA Web, Stanford HIVdb and HIV-TRACE) for data analyses so that laboratory personnel without extensive bioinformatics expertise could use it; making the approach accessible and affordable for labs worldwide. With more laboratories transitioning away from Sanger-based chemistries to NGS platforms, lower frequency drug resistance mutations (DRMs) can be detected, yet their clinical relevance is uncertain. We looked at the impact choice in cutoff percentage had on number of DRMs detected and found an inverse correlation between the two. Longitudinal studies will be needed to determine whether low frequency DRMs are an early indicator of emerging resistance. We successfully validated this pipeline against a commercial pipeline, and another free, publicly-available pipeline. RT DRM results from HyDRA Web were compared to both SmartGene and PASeq Web; using the Mantel test, R2 values were 0.9332 (p<0.0001) and 0.9097 (p<0.0001), respectively. PR and IN DRM results from HyDRA Web were then compared with PASeq Web only; using the Mantel test, R2 values were 0.9993 (p<0.0001) and 0.9765 (p<0.0001), respectively. Drug resistance was highest for the NRTI drug class and lowest for the PI drug class in this cohort. RT DRM interpretation reports from this pipeline were also highly correlative compared to SmartGene pipeline; using the Spearman's Correlation, rs value was 0.97757 (p<0.0001). HIV-TRACE was used to identify potential transmission clusters to better understand potential linkages among an urban cohort of persons living with HIV; more individuals were male, of black race, with an HIV risk factor of either MSM or High-risk Heterosexual. Common DRMs existed among individuals within a cluster. In summary, we validated a comprehensive, easy-to-use and affordable NGS approach for tracking HIV-1 drug resistance and identifying potential transmission clusters within the community.

Indexed as

AdultAnti-HIV AgentsCohort StudiesData AnalysisDistrict of ColumbiaDrug Resistance, ViralFemaleHigh-Throughput Nucleotide SequencingHIV-1HIV InfectionsHIV SeropositivityHomosexualityHumansLongitudinal StudiesMaleMiddle AgedAnti-HIV Agents

Identifiers

PMID30964884
PMCPMC6456221
OpenAlexW2938533346

What OpenQuestion holds

Textmetadata
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.