X4 tropic multi-drug resistant quasi-species detected at the time of primary HIV-1 infection remain exclusive or at least dominant far from PHI
Our objective was to analyze the evolution of resistance mutations (RM) and viral tropism of multi-drug-resistant (MDR) strains detected at primary HIV-1 infection (PHI). MDR HIV strain was defined as the presence of genotypic resistance to at least 1 antiretroviral of the 3 classes. Tropism determi...
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description | Our objective was to analyze the evolution of resistance mutations (RM) and viral tropism of multi-drug-resistant (MDR) strains detected at primary HIV-1 infection (PHI). MDR HIV strain was defined as the presence of genotypic resistance to at least 1 antiretroviral of the 3 classes. Tropism determinations (CCR5 or CXCR4) were performed on baseline plasma HIV-RNA and/or PBMC-HIV-DNA samples, then during follow-up using population-based sequencing of V3 loop and phenotypic tests. Clonal analysis was performed at baseline for env, RT and protease genes, and for HIV-DNA env gene during follow-up. Five patients were eligible. At baseline, RT, protease and env clones from HIV-RNA and HIV-DNA were highly homogenous for each patient; genotypic tropism was R5 in 3 (A,B,C) and X4 in 2 patients (D,E). MDR strains persisted in HIV-DNA throughout follow-up in all patients. For patient A, tropism remained R5 with concordance between phenotypic and genotypic tests. Clonal analysis on Month (M) 78 HIV-DNA evidenced exclusively R5 (21/21) variants. In patient B, clonal analysis at M36 showed exclusively R5 variants (19/19) using both genotypic and phenotypic tests. In patient C, baseline tropism was R5 by genotypic test and R5/X4 by phenotypic test. An expansion of these X4 clones was evidenced by clonal analysis on M72 HIV-DNA (12/14 X4 and 2/14 R5 variants). In patient D, baseline tropism was X4 with concordance between both techniques and HIV-RNA and HIV-DNA remained X4-tropic up to M72, confirmed by the clonal analysis. Patient E harboured highly homogenous X4-using population at baseline; tropism was unchanged at M1 and M18. In all patients, the initial MDR population was highly homogenous initially, supporting the early expansion of a monoclonal population and its long-term persistence. X4-tropic variants present at baseline were still exclusive (patients D and E) or dominant (at least one time point, patient C) far from PHI. |
doi_str_mv | 10.1371/journal.pone.0023301 |
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MDR HIV strain was defined as the presence of genotypic resistance to at least 1 antiretroviral of the 3 classes. Tropism determinations (CCR5 or CXCR4) were performed on baseline plasma HIV-RNA and/or PBMC-HIV-DNA samples, then during follow-up using population-based sequencing of V3 loop and phenotypic tests. Clonal analysis was performed at baseline for env, RT and protease genes, and for HIV-DNA env gene during follow-up. Five patients were eligible. At baseline, RT, protease and env clones from HIV-RNA and HIV-DNA were highly homogenous for each patient; genotypic tropism was R5 in 3 (A,B,C) and X4 in 2 patients (D,E). MDR strains persisted in HIV-DNA throughout follow-up in all patients. For patient A, tropism remained R5 with concordance between phenotypic and genotypic tests. Clonal analysis on Month (M) 78 HIV-DNA evidenced exclusively R5 (21/21) variants. In patient B, clonal analysis at M36 showed exclusively R5 variants (19/19) using both genotypic and phenotypic tests. In patient C, baseline tropism was R5 by genotypic test and R5/X4 by phenotypic test. An expansion of these X4 clones was evidenced by clonal analysis on M72 HIV-DNA (12/14 X4 and 2/14 R5 variants). In patient D, baseline tropism was X4 with concordance between both techniques and HIV-RNA and HIV-DNA remained X4-tropic up to M72, confirmed by the clonal analysis. Patient E harboured highly homogenous X4-using population at baseline; tropism was unchanged at M1 and M18. In all patients, the initial MDR population was highly homogenous initially, supporting the early expansion of a monoclonal population and its long-term persistence. X4-tropic variants present at baseline were still exclusive (patients D and E) or dominant (at least one time point, patient C) far from PHI.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0023301</identifier><identifier>PMID: 21887243</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; Adolescent ; Adult ; Aged ; AIDS ; Algorithms ; Antiretroviral agents ; Biology ; CCR5 protein ; Chemokines ; Cloning ; CXCR4 protein ; Deoxyribonucleic acid ; DNA ; DNA sequencing ; DNA, Viral - blood ; Drug resistance ; Drug Resistance, Multiple, Viral ; Env gene ; Female ; Gene sequencing ; Genes ; Genomes ; Genotype & phenotype ; Health aspects ; HIV ; HIV Infections - blood ; HIV Infections - virology ; HIV Reverse Transcriptase - genetics ; HIV-1 - enzymology ; HIV-1 - genetics ; HIV-1 - physiology ; Human immunodeficiency virus ; Humans ; Infections ; Longitudinal Studies ; Male ; Medicine ; Middle Aged ; Molecular Sequence Data ; Multidrug resistance ; Mutation ; Patients ; Peripheral blood mononuclear cells ; Phylogenetics ; Phylogeny ; Physics ; Plasma ; Polymerase chain reaction ; Protease ; Proteases ; Proteinase ; Ribonucleic acid ; RNA ; RNA, Viral - blood ; Strains (organisms) ; Tropism ; Viruses ; Young Adult</subject><ispartof>PloS one, 2011-08, Vol.6 (8), p.e23301-e23301</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Ghosn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Ghosn et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-b248a62a6e06f73092deae2825a5188aa73933668771a060c19436dfed2f8dd53</citedby><cites>FETCH-LOGICAL-c691t-b248a62a6e06f73092deae2825a5188aa73933668771a060c19436dfed2f8dd53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160852/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160852/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21887243$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ghosn, Jade</creatorcontrib><creatorcontrib>Galimand, Julie</creatorcontrib><creatorcontrib>Raymond, Stéphanie</creatorcontrib><creatorcontrib>Meyer, Laurence</creatorcontrib><creatorcontrib>Deveau, Christiane</creatorcontrib><creatorcontrib>Goujard, Cécile</creatorcontrib><creatorcontrib>Izopet, Jacques</creatorcontrib><creatorcontrib>Rouzioux, Christine</creatorcontrib><creatorcontrib>Chaix, Marie-Laure</creatorcontrib><creatorcontrib>ANRS CO 06 PRIMO cohort</creatorcontrib><creatorcontrib>for the ANRS CO 06 PRIMO cohort</creatorcontrib><title>X4 tropic multi-drug resistant quasi-species detected at the time of primary HIV-1 infection remain exclusive or at least dominant far from PHI</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Our objective was to analyze the evolution of resistance mutations (RM) and viral tropism of multi-drug-resistant (MDR) strains detected at primary HIV-1 infection (PHI). MDR HIV strain was defined as the presence of genotypic resistance to at least 1 antiretroviral of the 3 classes. Tropism determinations (CCR5 or CXCR4) were performed on baseline plasma HIV-RNA and/or PBMC-HIV-DNA samples, then during follow-up using population-based sequencing of V3 loop and phenotypic tests. Clonal analysis was performed at baseline for env, RT and protease genes, and for HIV-DNA env gene during follow-up. Five patients were eligible. At baseline, RT, protease and env clones from HIV-RNA and HIV-DNA were highly homogenous for each patient; genotypic tropism was R5 in 3 (A,B,C) and X4 in 2 patients (D,E). MDR strains persisted in HIV-DNA throughout follow-up in all patients. For patient A, tropism remained R5 with concordance between phenotypic and genotypic tests. Clonal analysis on Month (M) 78 HIV-DNA evidenced exclusively R5 (21/21) variants. In patient B, clonal analysis at M36 showed exclusively R5 variants (19/19) using both genotypic and phenotypic tests. In patient C, baseline tropism was R5 by genotypic test and R5/X4 by phenotypic test. An expansion of these X4 clones was evidenced by clonal analysis on M72 HIV-DNA (12/14 X4 and 2/14 R5 variants). In patient D, baseline tropism was X4 with concordance between both techniques and HIV-RNA and HIV-DNA remained X4-tropic up to M72, confirmed by the clonal analysis. Patient E harboured highly homogenous X4-using population at baseline; tropism was unchanged at M1 and M18. In all patients, the initial MDR population was highly homogenous initially, supporting the early expansion of a monoclonal population and its long-term persistence. X4-tropic variants present at baseline were still exclusive (patients D and E) or dominant (at least one time point, patient C) far from PHI.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>AIDS</subject><subject>Algorithms</subject><subject>Antiretroviral agents</subject><subject>Biology</subject><subject>CCR5 protein</subject><subject>Chemokines</subject><subject>Cloning</subject><subject>CXCR4 protein</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA sequencing</subject><subject>DNA, Viral - blood</subject><subject>Drug resistance</subject><subject>Drug Resistance, Multiple, Viral</subject><subject>Env gene</subject><subject>Female</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genomes</subject><subject>Genotype & phenotype</subject><subject>Health aspects</subject><subject>HIV</subject><subject>HIV Infections - blood</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 - physiology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infections</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Multidrug resistance</subject><subject>Mutation</subject><subject>Patients</subject><subject>Peripheral blood mononuclear cells</subject><subject>Phylogenetics</subject><subject>Phylogeny</subject><subject>Physics</subject><subject>Plasma</subject><subject>Polymerase chain reaction</subject><subject>Protease</subject><subject>Proteases</subject><subject>Proteinase</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Viral - blood</subject><subject>Strains 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BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ghosn, Jade</au><au>Galimand, Julie</au><au>Raymond, Stéphanie</au><au>Meyer, Laurence</au><au>Deveau, Christiane</au><au>Goujard, Cécile</au><au>Izopet, Jacques</au><au>Rouzioux, Christine</au><au>Chaix, Marie-Laure</au><aucorp>ANRS CO 06 PRIMO cohort</aucorp><aucorp>for the ANRS CO 06 PRIMO cohort</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>X4 tropic multi-drug resistant quasi-species detected at the time of primary HIV-1 infection remain exclusive or at least dominant far from PHI</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-08-24</date><risdate>2011</risdate><volume>6</volume><issue>8</issue><spage>e23301</spage><epage>e23301</epage><pages>e23301-e23301</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Our objective was to analyze the evolution of resistance mutations (RM) and viral tropism of multi-drug-resistant (MDR) strains detected at primary HIV-1 infection (PHI). MDR HIV strain was defined as the presence of genotypic resistance to at least 1 antiretroviral of the 3 classes. Tropism determinations (CCR5 or CXCR4) were performed on baseline plasma HIV-RNA and/or PBMC-HIV-DNA samples, then during follow-up using population-based sequencing of V3 loop and phenotypic tests. Clonal analysis was performed at baseline for env, RT and protease genes, and for HIV-DNA env gene during follow-up. Five patients were eligible. At baseline, RT, protease and env clones from HIV-RNA and HIV-DNA were highly homogenous for each patient; genotypic tropism was R5 in 3 (A,B,C) and X4 in 2 patients (D,E). MDR strains persisted in HIV-DNA throughout follow-up in all patients. For patient A, tropism remained R5 with concordance between phenotypic and genotypic tests. Clonal analysis on Month (M) 78 HIV-DNA evidenced exclusively R5 (21/21) variants. In patient B, clonal analysis at M36 showed exclusively R5 variants (19/19) using both genotypic and phenotypic tests. In patient C, baseline tropism was R5 by genotypic test and R5/X4 by phenotypic test. An expansion of these X4 clones was evidenced by clonal analysis on M72 HIV-DNA (12/14 X4 and 2/14 R5 variants). In patient D, baseline tropism was X4 with concordance between both techniques and HIV-RNA and HIV-DNA remained X4-tropic up to M72, confirmed by the clonal analysis. Patient E harboured highly homogenous X4-using population at baseline; tropism was unchanged at M1 and M18. In all patients, the initial MDR population was highly homogenous initially, supporting the early expansion of a monoclonal population and its long-term persistence. X4-tropic variants present at baseline were still exclusive (patients D and E) or dominant (at least one time point, patient C) far from PHI.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21887243</pmid><doi>10.1371/journal.pone.0023301</doi><tpages>e23301</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2011-08, Vol.6 (8), p.e23301-e23301 |
issn | 1932-6203 1932-6203 |
language | eng |
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source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Acquired immune deficiency syndrome Adolescent Adult Aged AIDS Algorithms Antiretroviral agents Biology CCR5 protein Chemokines Cloning CXCR4 protein Deoxyribonucleic acid DNA DNA sequencing DNA, Viral - blood Drug resistance Drug Resistance, Multiple, Viral Env gene Female Gene sequencing Genes Genomes Genotype & phenotype Health aspects HIV HIV Infections - blood HIV Infections - virology HIV Reverse Transcriptase - genetics HIV-1 - enzymology HIV-1 - genetics HIV-1 - physiology Human immunodeficiency virus Humans Infections Longitudinal Studies Male Medicine Middle Aged Molecular Sequence Data Multidrug resistance Mutation Patients Peripheral blood mononuclear cells Phylogenetics Phylogeny Physics Plasma Polymerase chain reaction Protease Proteases Proteinase Ribonucleic acid RNA RNA, Viral - blood Strains (organisms) Tropism Viruses Young Adult |
title | X4 tropic multi-drug resistant quasi-species detected at the time of primary HIV-1 infection remain exclusive or at least dominant far from PHI |
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