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2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?

BACKGROUND: Doravirine, rilpivirine, and etravirine are newer generation non-nucleoside reverse transcriptase inhibitors (NNRTI) that are intended to be more durable alternatives to efavirenz and nevirapine. We examined transmitted drug resistance (TDR) and acquired drug resistance (ADR) to NNRTIs f...

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Autores principales: Theresa Dungca, Nina, Schwem, Brian, Arevalo, Geraldine, Francisco, Christian, Penalosa-Ramos, Christine, Ching, Patrick, Leyritana, Katerina, Destura, Raul, Lim, Jodor, Tactacan-Abrenica, Rosario, Telan, Elizabeth, Solante, Rontgene, Samonte, Genesis, Trinidad, Lyka, Mendoza, Kevin, Alejandria, Marissa M, Salvana, Edsel Maurice T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810627/
http://dx.doi.org/10.1093/ofid/ofz360.2185
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author Theresa Dungca, Nina
Schwem, Brian
Arevalo, Geraldine
Francisco, Christian
Penalosa-Ramos, Christine
Ching, Patrick
Leyritana, Katerina
Destura, Raul
Lim, Jodor
Tactacan-Abrenica, Rosario
Telan, Elizabeth
Solante, Rontgene
Samonte, Genesis
Trinidad, Lyka
Mendoza, Kevin
Alejandria, Marissa M
Salvana, Edsel Maurice T
author_facet Theresa Dungca, Nina
Schwem, Brian
Arevalo, Geraldine
Francisco, Christian
Penalosa-Ramos, Christine
Ching, Patrick
Leyritana, Katerina
Destura, Raul
Lim, Jodor
Tactacan-Abrenica, Rosario
Telan, Elizabeth
Solante, Rontgene
Samonte, Genesis
Trinidad, Lyka
Mendoza, Kevin
Alejandria, Marissa M
Salvana, Edsel Maurice T
author_sort Theresa Dungca, Nina
collection PubMed
description BACKGROUND: Doravirine, rilpivirine, and etravirine are newer generation non-nucleoside reverse transcriptase inhibitors (NNRTI) that are intended to be more durable alternatives to efavirenz and nevirapine. We examined transmitted drug resistance (TDR) and acquired drug resistance (ADR) to NNRTIs from recent local TDR and ADR data to determine whether these can be useful as first-line or second-line antiretroviral (ARV) agents. METHODS: We reanalyzed Sanger-Based sequences (SBS) from an ADR surveillance study; and SBS and near-whole-genome next-generation sequences (NGS) from a TDR surveillance study using the Stanford HIV Drug Resistance Database. RESULTS: ADR: Out of 513 Filipino PLHIV from an ADR surveillance study on one year of ARV treatment, 53 (10.3%) failed (HIV VL >1,000 copies/mL). Among these, 48 had clinically significant mutations. Table 1 shows NNRTI ADR frequencies. There was no significant ADR difference between first-generation and newer generation NNRTIs. TDR: 298 treatment-naïve Filipino PLHIV underwent baselines sequencing. All 298 had SBS. 266 had successful NGS. Table 1 shows SBS and NGS TDR NNRTI resistance at a 5% minor variant cutoff. There was no significant TDR difference between first-generation and newer generation NNRTIs. CONCLUSION: ADR and TDR rates to the newer NNRTIs are similar to first-generation NNRTIs. High TDR to doravirine on NGS is concerning, but its clinical significance is unclear. Etravirine had the lowest TDR and ADR and may be the most useful new-generation NNRTI. However, integrase strand transfer inhibitor-based regimens will likely be more durable. [Image: see text] DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68106272019-10-28 2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option? Theresa Dungca, Nina Schwem, Brian Arevalo, Geraldine Francisco, Christian Penalosa-Ramos, Christine Ching, Patrick Leyritana, Katerina Destura, Raul Lim, Jodor Tactacan-Abrenica, Rosario Telan, Elizabeth Solante, Rontgene Samonte, Genesis Trinidad, Lyka Mendoza, Kevin Alejandria, Marissa M Salvana, Edsel Maurice T Open Forum Infect Dis Abstracts BACKGROUND: Doravirine, rilpivirine, and etravirine are newer generation non-nucleoside reverse transcriptase inhibitors (NNRTI) that are intended to be more durable alternatives to efavirenz and nevirapine. We examined transmitted drug resistance (TDR) and acquired drug resistance (ADR) to NNRTIs from recent local TDR and ADR data to determine whether these can be useful as first-line or second-line antiretroviral (ARV) agents. METHODS: We reanalyzed Sanger-Based sequences (SBS) from an ADR surveillance study; and SBS and near-whole-genome next-generation sequences (NGS) from a TDR surveillance study using the Stanford HIV Drug Resistance Database. RESULTS: ADR: Out of 513 Filipino PLHIV from an ADR surveillance study on one year of ARV treatment, 53 (10.3%) failed (HIV VL >1,000 copies/mL). Among these, 48 had clinically significant mutations. Table 1 shows NNRTI ADR frequencies. There was no significant ADR difference between first-generation and newer generation NNRTIs. TDR: 298 treatment-naïve Filipino PLHIV underwent baselines sequencing. All 298 had SBS. 266 had successful NGS. Table 1 shows SBS and NGS TDR NNRTI resistance at a 5% minor variant cutoff. There was no significant TDR difference between first-generation and newer generation NNRTIs. CONCLUSION: ADR and TDR rates to the newer NNRTIs are similar to first-generation NNRTIs. High TDR to doravirine on NGS is concerning, but its clinical significance is unclear. Etravirine had the lowest TDR and ADR and may be the most useful new-generation NNRTI. However, integrase strand transfer inhibitor-based regimens will likely be more durable. [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6810627/ http://dx.doi.org/10.1093/ofid/ofz360.2185 Text en © The Author(s) 2019. 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
Theresa Dungca, Nina
Schwem, Brian
Arevalo, Geraldine
Francisco, Christian
Penalosa-Ramos, Christine
Ching, Patrick
Leyritana, Katerina
Destura, Raul
Lim, Jodor
Tactacan-Abrenica, Rosario
Telan, Elizabeth
Solante, Rontgene
Samonte, Genesis
Trinidad, Lyka
Mendoza, Kevin
Alejandria, Marissa M
Salvana, Edsel Maurice T
2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?
title 2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?
title_full 2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?
title_fullStr 2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?
title_full_unstemmed 2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?
title_short 2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?
title_sort 2507. transmitted and acquired nnrti resistance in the philippines: are newer generation nnrtis a viable option?
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810627/
http://dx.doi.org/10.1093/ofid/ofz360.2185
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