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OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories

BACKGROUND: HIV drug resistance (HIVDR) testing can assist clinicians in selecting treatments. However, high complexity and cost of genotyping assays limit routine testing in settings where HIVDR prevalence has reached high levels. METHODS: The oligonucleotide ligation assay (OLA)-Simple kit was dev...

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Autores principales: Panpradist, Nuttada, Beck, Ingrid A., Vrana, Justin, Higa, Nikki, McIntyre, David, Ruth, Parker S., So, Isaac, Kline, Enos C., Kanthula, Ruth, Wong-On-Wing, Annie, Lim, Jonathan, Ko, Daisy, Milne, Ross, Rossouw, Theresa, Feucht, Ute D., Chung, Michael, Jourdain, Gonzague, Ngo-Giang-Huong, Nicole, Laomanit, Laddawan, Soria, Jaime, Lai, James, Klavins, Eric D., Frenkel, Lisa M., Lutz, Barry R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921160/
https://www.ncbi.nlm.nih.gov/pubmed/31767540
http://dx.doi.org/10.1016/j.ebiom.2019.11.002
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author Panpradist, Nuttada
Beck, Ingrid A.
Vrana, Justin
Higa, Nikki
McIntyre, David
Ruth, Parker S.
So, Isaac
Kline, Enos C.
Kanthula, Ruth
Wong-On-Wing, Annie
Lim, Jonathan
Ko, Daisy
Milne, Ross
Rossouw, Theresa
Feucht, Ute D.
Chung, Michael
Jourdain, Gonzague
Ngo-Giang-Huong, Nicole
Laomanit, Laddawan
Soria, Jaime
Lai, James
Klavins, Eric D.
Frenkel, Lisa M.
Lutz, Barry R.
author_facet Panpradist, Nuttada
Beck, Ingrid A.
Vrana, Justin
Higa, Nikki
McIntyre, David
Ruth, Parker S.
So, Isaac
Kline, Enos C.
Kanthula, Ruth
Wong-On-Wing, Annie
Lim, Jonathan
Ko, Daisy
Milne, Ross
Rossouw, Theresa
Feucht, Ute D.
Chung, Michael
Jourdain, Gonzague
Ngo-Giang-Huong, Nicole
Laomanit, Laddawan
Soria, Jaime
Lai, James
Klavins, Eric D.
Frenkel, Lisa M.
Lutz, Barry R.
author_sort Panpradist, Nuttada
collection PubMed
description BACKGROUND: HIV drug resistance (HIVDR) testing can assist clinicians in selecting treatments. However, high complexity and cost of genotyping assays limit routine testing in settings where HIVDR prevalence has reached high levels. METHODS: The oligonucleotide ligation assay (OLA)-Simple kit was developed for detection of HIVDR against first-line non-nucleoside/nucleoside reverse transcriptase inhibitors and validated on 672 codons (168 specimens) from subtypes A, B, C, D, and AE. The kit uses dry reagents to facilitate assay setup, lateral flow devices for visual HIVDR detections, and in-house software with an interface for guiding users and analyzing results. FINDINGS: HIVDR analysis of specimens by OLA-Simple compared to Sanger sequencing revealed 99.6 ± 0.3% specificity and 98.2 ± 0.9% sensitivity, and compared to high-sensitivity assays, 99.6 ± 0.6% specificity and 86.2 ± 2.5% sensitivity, with 2.6 ± 0.9% indeterminate results. OLA-Simple was performed more rapidly compared to Sanger sequencing (<4 h vs. 35–72 h). Forty-one untrained volunteers blindly tested two specimens each with 96.8 ± 0.8% accuracy. INTERPRETATION: OLA-Simple compares favorably with HIVDR genotyping by Sanger and sensitive comparators. Instructional software enabled inexperienced, first-time users to perform the assay with high accuracy. The reduced complexity, cost, and training requirements of OLA-Simple could improve access to HIVDR testing in low-resource settings and potentially allow same-day selection of appropriate antiretroviral therapy. FUND: USA National Institutes of Health R01; the Clinical and Retrovirology Research Core and the Molecular Profiling and Computational Biology Core of the UW CFAR; Seattle Children's Research Institute; UW Holloman Innovation Challenge Award; Pilcher Faculty Fellowship.
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spelling pubmed-69211602019-12-27 OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories Panpradist, Nuttada Beck, Ingrid A. Vrana, Justin Higa, Nikki McIntyre, David Ruth, Parker S. So, Isaac Kline, Enos C. Kanthula, Ruth Wong-On-Wing, Annie Lim, Jonathan Ko, Daisy Milne, Ross Rossouw, Theresa Feucht, Ute D. Chung, Michael Jourdain, Gonzague Ngo-Giang-Huong, Nicole Laomanit, Laddawan Soria, Jaime Lai, James Klavins, Eric D. Frenkel, Lisa M. Lutz, Barry R. EBioMedicine Research paper BACKGROUND: HIV drug resistance (HIVDR) testing can assist clinicians in selecting treatments. However, high complexity and cost of genotyping assays limit routine testing in settings where HIVDR prevalence has reached high levels. METHODS: The oligonucleotide ligation assay (OLA)-Simple kit was developed for detection of HIVDR against first-line non-nucleoside/nucleoside reverse transcriptase inhibitors and validated on 672 codons (168 specimens) from subtypes A, B, C, D, and AE. The kit uses dry reagents to facilitate assay setup, lateral flow devices for visual HIVDR detections, and in-house software with an interface for guiding users and analyzing results. FINDINGS: HIVDR analysis of specimens by OLA-Simple compared to Sanger sequencing revealed 99.6 ± 0.3% specificity and 98.2 ± 0.9% sensitivity, and compared to high-sensitivity assays, 99.6 ± 0.6% specificity and 86.2 ± 2.5% sensitivity, with 2.6 ± 0.9% indeterminate results. OLA-Simple was performed more rapidly compared to Sanger sequencing (<4 h vs. 35–72 h). Forty-one untrained volunteers blindly tested two specimens each with 96.8 ± 0.8% accuracy. INTERPRETATION: OLA-Simple compares favorably with HIVDR genotyping by Sanger and sensitive comparators. Instructional software enabled inexperienced, first-time users to perform the assay with high accuracy. The reduced complexity, cost, and training requirements of OLA-Simple could improve access to HIVDR testing in low-resource settings and potentially allow same-day selection of appropriate antiretroviral therapy. FUND: USA National Institutes of Health R01; the Clinical and Retrovirology Research Core and the Molecular Profiling and Computational Biology Core of the UW CFAR; Seattle Children's Research Institute; UW Holloman Innovation Challenge Award; Pilcher Faculty Fellowship. Elsevier 2019-11-22 /pmc/articles/PMC6921160/ /pubmed/31767540 http://dx.doi.org/10.1016/j.ebiom.2019.11.002 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Panpradist, Nuttada
Beck, Ingrid A.
Vrana, Justin
Higa, Nikki
McIntyre, David
Ruth, Parker S.
So, Isaac
Kline, Enos C.
Kanthula, Ruth
Wong-On-Wing, Annie
Lim, Jonathan
Ko, Daisy
Milne, Ross
Rossouw, Theresa
Feucht, Ute D.
Chung, Michael
Jourdain, Gonzague
Ngo-Giang-Huong, Nicole
Laomanit, Laddawan
Soria, Jaime
Lai, James
Klavins, Eric D.
Frenkel, Lisa M.
Lutz, Barry R.
OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories
title OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories
title_full OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories
title_fullStr OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories
title_full_unstemmed OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories
title_short OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories
title_sort ola-simple: a software-guided hiv-1 drug resistance test for low-resource laboratories
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921160/
https://www.ncbi.nlm.nih.gov/pubmed/31767540
http://dx.doi.org/10.1016/j.ebiom.2019.11.002
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