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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Veröffentlicht in:PloS one 2011-08, Vol.6 (8), p.e23301-e23301
Hauptverfasser: Ghosn, Jade, Galimand, Julie, Raymond, Stéphanie, Meyer, Laurence, Deveau, Christiane, Goujard, Cécile, Izopet, Jacques, Rouzioux, Christine, Chaix, Marie-Laure
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container_title PloS one
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creator Ghosn, Jade
Galimand, Julie
Raymond, Stéphanie
Meyer, Laurence
Deveau, Christiane
Goujard, Cécile
Izopet, Jacques
Rouzioux, Christine
Chaix, Marie-Laure
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 &amp; 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 &amp; 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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Collection</collection><collection>Biotechnology and 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>
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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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