date: 2018-01-19T13:37:57Z pdf:PDFVersion: 1.5 pdf:docinfo:title: Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals xmp:CreatorTool: LaTeX with hyperref package access_permission:can_print_degraded: true subject: The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected individuals. RNase H sequences from 112 NRTI treated but virologically failing individuals and 28 antiretroviral therapy (ART)-naive individuals were generated and analysed. In addition, sequences from 359 subtype C ART-naive sequences were downloaded from Los Alamos database to give a total of 387 sequences from ART-naive individuals for the analysis. Fisher?s exact test was used to identify mutations and Bayesian network learning was applied to identify novel NRTI resistance mutation pathways in RNase H domain. The mutations A435L, S468A, T470S, L484I, A508S, Q509L, L517I, Q524E and E529D were more prevalent in sequences from treatment-experienced compared to antiretroviral treatment naive individuals, however, only the E529D mutation remained significant after correction for multiple comparison. Our findings suggest a potential interaction between E529D and NRTI-treatment; however, site-directed mutagenesis is needed to understand the impact of this RNase H mutation. dc:format: application/pdf; version=1.5 pdf:docinfo:creator_tool: LaTeX with hyperref package access_permission:fill_in_form: true pdf:encrypted: false dc:title: Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals modified: 2018-01-19T13:37:57Z cp:subject: The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected individuals. RNase H sequences from 112 NRTI treated but virologically failing individuals and 28 antiretroviral therapy (ART)-naive individuals were generated and analysed. In addition, sequences from 359 subtype C ART-naive sequences were downloaded from Los Alamos database to give a total of 387 sequences from ART-naive individuals for the analysis. Fisher?s exact test was used to identify mutations and Bayesian network learning was applied to identify novel NRTI resistance mutation pathways in RNase H domain. The mutations A435L, S468A, T470S, L484I, A508S, Q509L, L517I, Q524E and E529D were more prevalent in sequences from treatment-experienced compared to antiretroviral treatment naive individuals, however, only the E529D mutation remained significant after correction for multiple comparison. Our findings suggest a potential interaction between E529D and NRTI-treatment; however, site-directed mutagenesis is needed to understand the impact of this RNase H mutation. pdf:docinfo:subject: The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected individuals. RNase H sequences from 112 NRTI treated but virologically failing individuals and 28 antiretroviral therapy (ART)-naive individuals were generated and analysed. In addition, sequences from 359 subtype C ART-naive sequences were downloaded from Los Alamos database to give a total of 387 sequences from ART-naive individuals for the analysis. Fisher?s exact test was used to identify mutations and Bayesian network learning was applied to identify novel NRTI resistance mutation pathways in RNase H domain. The mutations A435L, S468A, T470S, L484I, A508S, Q509L, L517I, Q524E and E529D were more prevalent in sequences from treatment-experienced compared to antiretroviral treatment naive individuals, however, only the E529D mutation remained significant after correction for multiple comparison. Our findings suggest a potential interaction between E529D and NRTI-treatment; however, site-directed mutagenesis is needed to understand the impact of this RNase H mutation. pdf:docinfo:creator: Sinaye Ngcapu, Kristof Theys, Pieter Libin, Vincent C. Marconi, Henry Sunpath, Thumbi Ndung?u and Michelle L. Gordon PTEX.Fullbanner: This is pdfTeX, Version 3.14159265-2.6-1.40.15 (TeX Live 2014/W32TeX) kpathsea version 6.2.0 meta:author: Sinaye Ngcapu, Kristof Theys, Pieter Libin, Vincent C. Marconi, Henry Sunpath, Thumbi Ndung?u and Michelle L. Gordon trapped: False meta:creation-date: 2017-11-08T09:54:15Z created: 2017-11-08T09:54:15Z access_permission:extract_for_accessibility: true Creation-Date: 2017-11-08T09:54:15Z Author: Sinaye Ngcapu, Kristof Theys, Pieter Libin, Vincent C. Marconi, Henry Sunpath, Thumbi Ndung?u and Michelle L. Gordon producer: pdfTeX-1.40.15 pdf:docinfo:producer: pdfTeX-1.40.15 pdf:unmappedUnicodeCharsPerPage: 0 dc:description: The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected individuals. RNase H sequences from 112 NRTI treated but virologically failing individuals and 28 antiretroviral therapy (ART)-naive individuals were generated and analysed. In addition, sequences from 359 subtype C ART-naive sequences were downloaded from Los Alamos database to give a total of 387 sequences from ART-naive individuals for the analysis. Fisher?s exact test was used to identify mutations and Bayesian network learning was applied to identify novel NRTI resistance mutation pathways in RNase H domain. The mutations A435L, S468A, T470S, L484I, A508S, Q509L, L517I, Q524E and E529D were more prevalent in sequences from treatment-experienced compared to antiretroviral treatment naive individuals, however, only the E529D mutation remained significant after correction for multiple comparison. Our findings suggest a potential interaction between E529D and NRTI-treatment; however, site-directed mutagenesis is needed to understand the impact of this RNase H mutation. Keywords: HIV-1; RNase H; resistance; mutations; NRTIs access_permission:modify_annotations: true dc:creator: Sinaye Ngcapu, Kristof Theys, Pieter Libin, Vincent C. Marconi, Henry Sunpath, Thumbi Ndung?u and Michelle L. Gordon description: The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected individuals. RNase H sequences from 112 NRTI treated but virologically failing individuals and 28 antiretroviral therapy (ART)-naive individuals were generated and analysed. In addition, sequences from 359 subtype C ART-naive sequences were downloaded from Los Alamos database to give a total of 387 sequences from ART-naive individuals for the analysis. Fisher?s exact test was used to identify mutations and Bayesian network learning was applied to identify novel NRTI resistance mutation pathways in RNase H domain. The mutations A435L, S468A, T470S, L484I, A508S, Q509L, L517I, Q524E and E529D were more prevalent in sequences from treatment-experienced compared to antiretroviral treatment naive individuals, however, only the E529D mutation remained significant after correction for multiple comparison. Our findings suggest a potential interaction between E529D and NRTI-treatment; however, site-directed mutagenesis is needed to understand the impact of this RNase H mutation. dcterms:created: 2017-11-08T09:54:15Z Last-Modified: 2018-01-19T13:37:57Z dcterms:modified: 2018-01-19T13:37:57Z title: Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals xmpMM:DocumentID: uuid:e06a7a91-f475-46bc-a837-78059b753a7a Last-Save-Date: 2018-01-19T13:37:57Z pdf:docinfo:keywords: HIV-1; RNase H; resistance; mutations; NRTIs pdf:docinfo:modified: 2018-01-19T13:37:57Z meta:save-date: 2018-01-19T13:37:57Z pdf:docinfo:custom:PTEX.Fullbanner: This is pdfTeX, Version 3.14159265-2.6-1.40.15 (TeX Live 2014/W32TeX) kpathsea version 6.2.0 Content-Type: application/pdf X-Parsed-By: org.apache.tika.parser.DefaultParser creator: Sinaye Ngcapu, Kristof Theys, Pieter Libin, Vincent C. Marconi, Henry Sunpath, Thumbi Ndung?u and Michelle L. Gordon dc:subject: HIV-1; RNase H; resistance; mutations; NRTIs access_permission:assemble_document: true xmpTPg:NPages: 10 pdf:charsPerPage: 2881 access_permission:extract_content: true access_permission:can_print: true pdf:docinfo:trapped: False meta:keyword: HIV-1; RNase H; resistance; mutations; NRTIs access_permission:can_modify: true pdf:docinfo:created: 2017-11-08T09:54:15Z