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1282. Detection of HIV Transmitted Drug Resistance by Next-Generation Sequencing in a CRF01_AE Predominant Epidemic

BACKGROUND: The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. Concurrent with this is a subtype shift from B to CRF01_AE. We have previously documented transmitted drug resistance (TDR) locally. However, the lack of drug pressure and the insensitivity of Sanger-based sequenci...

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Autores principales: Salvana, Edsel Maurice, Dungca, Nina, Arevalo, Geraldine, Leyritana, Katerina, Francisco, Christian, Penalosa, Christine, Destura, Raul, Lim, Jodor, Schwem, Brian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253099/
http://dx.doi.org/10.1093/ofid/ofy210.1115
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author Salvana, Edsel Maurice
Dungca, Nina
Arevalo, Geraldine
Leyritana, Katerina
Francisco, Christian
Penalosa, Christine
Destura, Raul
Lim, Jodor
Schwem, Brian
author_facet Salvana, Edsel Maurice
Dungca, Nina
Arevalo, Geraldine
Leyritana, Katerina
Francisco, Christian
Penalosa, Christine
Destura, Raul
Lim, Jodor
Schwem, Brian
author_sort Salvana, Edsel Maurice
collection PubMed
description BACKGROUND: The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. Concurrent with this is a subtype shift from B to CRF01_AE. We have previously documented transmitted drug resistance (TDR) locally. However, the lack of drug pressure and the insensitivity of Sanger-based sequencing (SBS) may leave archived drug-resistance mutations (DRMs) undetected. To better detect TDR, we performed next-generation sequencing (NGS) on treatment-naïve patients and compared this with SBS. METHODS: Following ethics approval, newly-diagnosed adult Filipino HIV patients were recruited from the Philippine General Hospital HIV treatment hub. Demographic data were collected, and blood samples underwent SBS with a WHO-approved protocol. Whole-genome NGS was performed using Illumina HiSeq through a commercial provider (Macrogen, Korea). Genotype and DRMs were analyzed and scored using the Stanford HIV Drug Resistance Database. RESULTS: 113 patients were analyzed. Median age was 29 years (range 19–68), mean CD4 count was 147 cells/µL (range 0–556) and median viral load was 2.8 × 10(6) copies/mL. Genotype distribution was: CRF01_AE (93), B (13), possible CRF01_AE/B recombinants (5), CRF02_AG (1), possible URF (1). TDR prevalence by SBS and NGS at different minority variant cutoffs are shown in Table 1. All DRMs on SBS were found on NGS. Some samples had multiple DRMs. No factors were significantly associated with TDR, genotype, viral load or baseline CD4 count. CONCLUSION: NGS is a more sensitive tool for detecting TDR compared with SBS. Nearly double the DRMs were found at an NGS cutoff of ≥5%, including INSTI DRMs. With increasing HIV drug resistance worldwide, switching to NGS may help decrease rates of initial treatment failure, especially in settings with limited repertoires of ARVs. DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-62530992018-11-28 1282. Detection of HIV Transmitted Drug Resistance by Next-Generation Sequencing in a CRF01_AE Predominant Epidemic Salvana, Edsel Maurice Dungca, Nina Arevalo, Geraldine Leyritana, Katerina Francisco, Christian Penalosa, Christine Destura, Raul Lim, Jodor Schwem, Brian Open Forum Infect Dis Abstracts BACKGROUND: The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. Concurrent with this is a subtype shift from B to CRF01_AE. We have previously documented transmitted drug resistance (TDR) locally. However, the lack of drug pressure and the insensitivity of Sanger-based sequencing (SBS) may leave archived drug-resistance mutations (DRMs) undetected. To better detect TDR, we performed next-generation sequencing (NGS) on treatment-naïve patients and compared this with SBS. METHODS: Following ethics approval, newly-diagnosed adult Filipino HIV patients were recruited from the Philippine General Hospital HIV treatment hub. Demographic data were collected, and blood samples underwent SBS with a WHO-approved protocol. Whole-genome NGS was performed using Illumina HiSeq through a commercial provider (Macrogen, Korea). Genotype and DRMs were analyzed and scored using the Stanford HIV Drug Resistance Database. RESULTS: 113 patients were analyzed. Median age was 29 years (range 19–68), mean CD4 count was 147 cells/µL (range 0–556) and median viral load was 2.8 × 10(6) copies/mL. Genotype distribution was: CRF01_AE (93), B (13), possible CRF01_AE/B recombinants (5), CRF02_AG (1), possible URF (1). TDR prevalence by SBS and NGS at different minority variant cutoffs are shown in Table 1. All DRMs on SBS were found on NGS. Some samples had multiple DRMs. No factors were significantly associated with TDR, genotype, viral load or baseline CD4 count. CONCLUSION: NGS is a more sensitive tool for detecting TDR compared with SBS. Nearly double the DRMs were found at an NGS cutoff of ≥5%, including INSTI DRMs. With increasing HIV drug resistance worldwide, switching to NGS may help decrease rates of initial treatment failure, especially in settings with limited repertoires of ARVs. DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2018-11-26 /pmc/articles/PMC6253099/ http://dx.doi.org/10.1093/ofid/ofy210.1115 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Salvana, Edsel Maurice
Dungca, Nina
Arevalo, Geraldine
Leyritana, Katerina
Francisco, Christian
Penalosa, Christine
Destura, Raul
Lim, Jodor
Schwem, Brian
1282. Detection of HIV Transmitted Drug Resistance by Next-Generation Sequencing in a CRF01_AE Predominant Epidemic
title 1282. Detection of HIV Transmitted Drug Resistance by Next-Generation Sequencing in a CRF01_AE Predominant Epidemic
title_full 1282. Detection of HIV Transmitted Drug Resistance by Next-Generation Sequencing in a CRF01_AE Predominant Epidemic
title_fullStr 1282. Detection of HIV Transmitted Drug Resistance by Next-Generation Sequencing in a CRF01_AE Predominant Epidemic
title_full_unstemmed 1282. Detection of HIV Transmitted Drug Resistance by Next-Generation Sequencing in a CRF01_AE Predominant Epidemic
title_short 1282. Detection of HIV Transmitted Drug Resistance by Next-Generation Sequencing in a CRF01_AE Predominant Epidemic
title_sort 1282. detection of hiv transmitted drug resistance by next-generation sequencing in a crf01_ae predominant epidemic
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253099/
http://dx.doi.org/10.1093/ofid/ofy210.1115
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