Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients
The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients. We performed a large retrospective study to determine the number of treatment failures that...
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Veröffentlicht in: | AIDS (London) 2014-09, Vol.28 (15), p.2231-2239 |
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creator | Metzner, Karin J Scherrer, Alexandra U von Wyl, Viktor Böni, Jürg Yerly, Sabine Klimkait, Thomas Aubert, Vincent Furrer, Hansjakob Hirsch, Hans H Vernazza, Pietro L Cavassini, Matthias Calmy, Alexandra Bernasconi, Enos Weber, Rainer Günthard, Huldrych F |
description | The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients.
We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing.
Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients.
Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant.
As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered. |
doi_str_mv | 10.1097/QAD.0000000000000397 |
format | Article |
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We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing.
Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients.
Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant.
As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.</description><identifier>ISSN: 0269-9370</identifier><identifier>EISSN: 1473-5571</identifier><identifier>DOI: 10.1097/QAD.0000000000000397</identifier><identifier>PMID: 25036184</identifier><language>eng</language><publisher>England</publisher><subject>Adult ; AIDS/HIV ; Alleles ; Anti-Retroviral Agents - therapeutic use ; Drug Resistance, Viral ; Female ; Genotyping Techniques - methods ; HIV Infections - virology ; HIV Reverse Transcriptase - genetics ; HIV-1 - enzymology ; HIV-1 - genetics ; HIV-1 - isolation & purification ; Human immunodeficiency virus 1 ; Humans ; Lentivirus ; Male ; Microbial Sensitivity Tests - methods ; Middle Aged ; Mutation, Missense ; Retrospective Studies ; Retroviridae ; Treatment Outcome</subject><ispartof>AIDS (London), 2014-09, Vol.28 (15), p.2231-2239</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-f7b47cacdb36ea5f388196ad7863219795cc9fa37b6f3c2e805b1638f452fc263</citedby><cites>FETCH-LOGICAL-c456t-f7b47cacdb36ea5f388196ad7863219795cc9fa37b6f3c2e805b1638f452fc263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25036184$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Metzner, Karin J</creatorcontrib><creatorcontrib>Scherrer, Alexandra U</creatorcontrib><creatorcontrib>von Wyl, Viktor</creatorcontrib><creatorcontrib>Böni, Jürg</creatorcontrib><creatorcontrib>Yerly, Sabine</creatorcontrib><creatorcontrib>Klimkait, Thomas</creatorcontrib><creatorcontrib>Aubert, Vincent</creatorcontrib><creatorcontrib>Furrer, Hansjakob</creatorcontrib><creatorcontrib>Hirsch, Hans H</creatorcontrib><creatorcontrib>Vernazza, Pietro L</creatorcontrib><creatorcontrib>Cavassini, Matthias</creatorcontrib><creatorcontrib>Calmy, Alexandra</creatorcontrib><creatorcontrib>Bernasconi, Enos</creatorcontrib><creatorcontrib>Weber, Rainer</creatorcontrib><creatorcontrib>Günthard, Huldrych F</creatorcontrib><creatorcontrib>Swiss HIV Cohort Study</creatorcontrib><title>Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients</title><title>AIDS (London)</title><addtitle>AIDS</addtitle><description>The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients.
We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing.
Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients.
Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant.
As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.</description><subject>Adult</subject><subject>AIDS/HIV</subject><subject>Alleles</subject><subject>Anti-Retroviral Agents - therapeutic use</subject><subject>Drug Resistance, Viral</subject><subject>Female</subject><subject>Genotyping Techniques - methods</subject><subject>HIV Infections - virology</subject><subject>HIV Reverse Transcriptase - genetics</subject><subject>HIV-1 - enzymology</subject><subject>HIV-1 - genetics</subject><subject>HIV-1 - isolation & purification</subject><subject>Human immunodeficiency virus 1</subject><subject>Humans</subject><subject>Lentivirus</subject><subject>Male</subject><subject>Microbial Sensitivity Tests - methods</subject><subject>Middle Aged</subject><subject>Mutation, Missense</subject><subject>Retrospective Studies</subject><subject>Retroviridae</subject><subject>Treatment Outcome</subject><issn>0269-9370</issn><issn>1473-5571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1TAQhS0EopfCGyDkJZsUO078s6wu5UdcFVUqC1aR44zLoMQOtu-V7vPwojVtQYgN3oylOWfOaD5CXnJ2xplRb67O356xv58w6hHZ8E6Jpu8Vf0w2rJWmMUKxE_Is5-9V0zOtn5KTtmdCct1tyM8dLlhgom7GgM7OdIQAHguNni4YYsJypJ84E5fUhol-5Zpvm4NNaEOhExRwBWOgGKidJrz7l0hT3BcMQG8gxHJc0dEEGXOxwQEtkGvz5s4TCiYoKR4w1ezyDZJdj02weAC62oIQSn5Onng7Z3jxUE_Jl3cX19sPze7z-4_b813jul6WxquxU866aRQSbO-F1txIOyktRcuNMr1zxluhRumFa0GzfuRSaN_1rXetFKfk9f3cNcUf-7rksGB2MM82QNzngatqYfUU7P9SyVtT41tTpd291KWYcwI_rAkXm44DZ8MvkkMlOfxLstpePSTsxwWmP6bf6MQtPdqblw</recordid><startdate>20140924</startdate><enddate>20140924</enddate><creator>Metzner, Karin J</creator><creator>Scherrer, Alexandra U</creator><creator>von Wyl, Viktor</creator><creator>Böni, Jürg</creator><creator>Yerly, Sabine</creator><creator>Klimkait, Thomas</creator><creator>Aubert, Vincent</creator><creator>Furrer, Hansjakob</creator><creator>Hirsch, Hans H</creator><creator>Vernazza, Pietro L</creator><creator>Cavassini, Matthias</creator><creator>Calmy, Alexandra</creator><creator>Bernasconi, Enos</creator><creator>Weber, Rainer</creator><creator>Günthard, Huldrych F</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T2</scope><scope>7T5</scope><scope>7U2</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20140924</creationdate><title>Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients</title><author>Metzner, Karin J ; 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We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing.
Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients.
Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant.
As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.</abstract><cop>England</cop><pmid>25036184</pmid><doi>10.1097/QAD.0000000000000397</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult AIDS/HIV Alleles Anti-Retroviral Agents - therapeutic use Drug Resistance, Viral Female Genotyping Techniques - methods HIV Infections - virology HIV Reverse Transcriptase - genetics HIV-1 - enzymology HIV-1 - genetics HIV-1 - isolation & purification Human immunodeficiency virus 1 Humans Lentivirus Male Microbial Sensitivity Tests - methods Middle Aged Mutation, Missense Retrospective Studies Retroviridae Treatment Outcome |
title | Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients |
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