Correlation between genotypic (V3 population sequencing) and phenotypic (Trofile ES) methods of characterizing co-receptor usage of HIV-1 from 200 treatment-naïve HIV patients screened for Study A4001078
► Assessment of tropism is needed to identify patients likely to respond to maraviroc. ► Concordance between tropism testing methods in screening samples was determined. ► Phenotypic and genotypic methods reported similar frequencies of R5 and non-R5 virus. ► Most samples had non-R5 HIV-1 RNA levels...
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| Veröffentlicht in: | Antiviral research 2013-01, Vol.97 (1), p.60-65 |
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| creator | Portsmouth, Simon Valluri, Srinivas Rao Däumer, Martin Thiele, Bernhard Valdez, Hernan Lewis, Marilyn Craig, Charles Thielen, Alexander James, Ian Demarest, James Heera, Jayvant |
| description | ► Assessment of tropism is needed to identify patients likely to respond to maraviroc. ► Concordance between tropism testing methods in screening samples was determined. ► Phenotypic and genotypic methods reported similar frequencies of R5 and non-R5 virus. ► Most samples had non-R5 HIV-1 RNA levels of |
| doi_str_mv | 10.1016/j.antiviral.2012.11.002 |
| format | Article |
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Assessment of HIV-1 co-receptor usage is essential to identify patients who are likely to respond to maraviroc (MVC)-containing regimens. Co-receptor usage of plasma virus from all treatment-naïve patients screened for a MVC clinical trial was assessed using phenotypic and genotypic methodologies to evaluate concordance between testing methods and to assess the quantity of CXCR4-using (non-R5) virus in samples giving discordant results. Co-receptor usage was prospectively measured using the enhanced sensitivity Trofile assay (Trofile ES) to screen patients for enrollment in Study A4001078. Population and deep sequencing methodologies were utilized retrospectively to analyze all screening samples, with co-receptor usage determined using the geno2pheno algorithm. Concordance between methods was explored using descriptive statistics. The quantity of non-R5 virus in all samples was measured using deep sequencing. Trofile ES and matched genotype results were obtained for 199screening samples. Concordance of Trofile ES with population genotyping (5.75% false-positive rate [FPR]) and deep sequencing (3.5% FPR; 2% non-R5 threshold) was 91.7% and 89.6%, respectively. Population genotype data were available for all samples with non-reportable Trofile ES results; the distribution of co-receptor usage in this set was consistent with that in the overall population: 75% (12/16) R5 and 25% (4/16) non-R5. The majority of samples contained non-R5 plasma HIV-1 RNA estimated at either <1 log10 (62.0%) or ⩾4 log10 (30.5%) copies/mL; the absolute amount of detectable non-R5 virus remained stable between screening and baseline visits. Samples originally classified as non-R5 by Trofile ES but R5 by population sequencing had a relatively low absolute amount of non-R5 virus (mean 2.1%, median 0.1%). The determination of co-receptor usage using either Trofile ES or genotyping methodologies showed similar frequencies of R5 and non-R5 virus in this treatment-naïve study population. For both concordant and discordant samples, population sequencing appropriately identified R5 samples with low levels of non-R5-using virus.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/j.antiviral.2012.11.002</identifier><identifier>PMID: 23165088</identifier><identifier>CODEN: ARSRDR</identifier><language>eng</language><publisher>Kidlington: Elsevier B.V</publisher><subject>Algorithms ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; Clinical trials ; CXCR5 ; Data processing ; Genotype ; Genotypes ; Genotyping ; High-Throughput Nucleotide Sequencing - methods ; HIV Infections - virology ; HIV-1 ; HIV-1 - genetics ; HIV-1 - isolation & purification ; HIV-1 - physiology ; Human immunodeficiency virus 1 ; Human viral diseases ; Humans ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; Infectious diseases ; Maraviroc ; Medical sciences ; Pharmacology. Drug treatments ; Phenotype ; Population studies ; Prospective Studies ; Receptors, HIV - analysis ; RNA ; RNA, Viral - genetics ; Statistics ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Virology - methods ; Virus Attachment</subject><ispartof>Antiviral research, 2013-01, Vol.97 (1), p.60-65</ispartof><rights>2012 Elsevier B.V.</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-17b644b627a0e351668a622751bd922f5680d95b3537f38d24da4e37a1bafd6e3</citedby><cites>FETCH-LOGICAL-c434t-17b644b627a0e351668a622751bd922f5680d95b3537f38d24da4e37a1bafd6e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0166354212002574$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,4010,27900,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26830966$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23165088$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Portsmouth, Simon</creatorcontrib><creatorcontrib>Valluri, Srinivas Rao</creatorcontrib><creatorcontrib>Däumer, Martin</creatorcontrib><creatorcontrib>Thiele, Bernhard</creatorcontrib><creatorcontrib>Valdez, Hernan</creatorcontrib><creatorcontrib>Lewis, Marilyn</creatorcontrib><creatorcontrib>Craig, Charles</creatorcontrib><creatorcontrib>Thielen, Alexander</creatorcontrib><creatorcontrib>James, Ian</creatorcontrib><creatorcontrib>Demarest, James</creatorcontrib><creatorcontrib>Heera, Jayvant</creatorcontrib><title>Correlation between genotypic (V3 population sequencing) and phenotypic (Trofile ES) methods of characterizing co-receptor usage of HIV-1 from 200 treatment-naïve HIV patients screened for Study A4001078</title><title>Antiviral research</title><addtitle>Antiviral Res</addtitle><description>► Assessment of tropism is needed to identify patients likely to respond to maraviroc. ► Concordance between tropism testing methods in screening samples was determined. ► Phenotypic and genotypic methods reported similar frequencies of R5 and non-R5 virus. ► Most samples had non-R5 HIV-1 RNA levels of <1 log10 or ⩾4 log10copies/mL. ► V3 genotyping is subject to fewer non-reportable results than phenotypic testing.
Assessment of HIV-1 co-receptor usage is essential to identify patients who are likely to respond to maraviroc (MVC)-containing regimens. Co-receptor usage of plasma virus from all treatment-naïve patients screened for a MVC clinical trial was assessed using phenotypic and genotypic methodologies to evaluate concordance between testing methods and to assess the quantity of CXCR4-using (non-R5) virus in samples giving discordant results. Co-receptor usage was prospectively measured using the enhanced sensitivity Trofile assay (Trofile ES) to screen patients for enrollment in Study A4001078. Population and deep sequencing methodologies were utilized retrospectively to analyze all screening samples, with co-receptor usage determined using the geno2pheno algorithm. Concordance between methods was explored using descriptive statistics. The quantity of non-R5 virus in all samples was measured using deep sequencing. Trofile ES and matched genotype results were obtained for 199screening samples. Concordance of Trofile ES with population genotyping (5.75% false-positive rate [FPR]) and deep sequencing (3.5% FPR; 2% non-R5 threshold) was 91.7% and 89.6%, respectively. Population genotype data were available for all samples with non-reportable Trofile ES results; the distribution of co-receptor usage in this set was consistent with that in the overall population: 75% (12/16) R5 and 25% (4/16) non-R5. The majority of samples contained non-R5 plasma HIV-1 RNA estimated at either <1 log10 (62.0%) or ⩾4 log10 (30.5%) copies/mL; the absolute amount of detectable non-R5 virus remained stable between screening and baseline visits. Samples originally classified as non-R5 by Trofile ES but R5 by population sequencing had a relatively low absolute amount of non-R5 virus (mean 2.1%, median 0.1%). The determination of co-receptor usage using either Trofile ES or genotyping methodologies showed similar frequencies of R5 and non-R5 virus in this treatment-naïve study population. For both concordant and discordant samples, population sequencing appropriately identified R5 samples with low levels of non-R5-using virus.</description><subject>Algorithms</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Clinical trials</subject><subject>CXCR5</subject><subject>Data processing</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Genotyping</subject><subject>High-Throughput Nucleotide Sequencing - methods</subject><subject>HIV Infections - virology</subject><subject>HIV-1</subject><subject>HIV-1 - genetics</subject><subject>HIV-1 - isolation & purification</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus 1</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunodeficiencies</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Infectious diseases</subject><subject>Maraviroc</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenotype</subject><subject>Population studies</subject><subject>Prospective Studies</subject><subject>Receptors, HIV - analysis</subject><subject>RNA</subject><subject>RNA, Viral - genetics</subject><subject>Statistics</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Virology - methods</subject><subject>Virus Attachment</subject><issn>0166-3542</issn><issn>1872-9096</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks9u1DAQhyMEokvhFcAXpPaQ4D-JnRxXq0IrVeLQ0qvl2JNdr5I42M5Wy0vxEFx5KLzapT3CyZL9zXj0-ybLPhBcEEz4p22hxmh31qu-oJjQgpACY_oiW5Ba0LzBDX-ZLRLJc1aV9Cx7E8IWY8xFU7_OzigjvMJ1vch-r5z30Kto3YhaiI8AI1rD6OJ-shpdPDA0uWk-AQG-zzBqO64vkRoNmjbP5L13ne0BXd1dogHixpmAXIf0RnmlI3j7I5Uh7XIPGqboPJqDWsOBub55yAnqvBsQxRhFDyoOMMZ8VL9-7uDwjqY0QboKKGifZgSDutTiLs5mj5YlxgSL-m32qlN9gHen8zz79vnqfnWd3379crNa3ua6ZGXMiWh5WbacCoWBVSmkWnFKRUVa01DaVbzGpqlaVjHRsdrQ0qgSmFCkVZ3hwM6zi2PfybsUSIhysEFD36sR3BwkoYJRQmhV_w9KBcG0aRIqjqj2LgQPnZy8HZTfS4Llwbrcyifr8mBdEiKT9VT5_vTJ3A5gnur-ak7AxxOgglZ951WSGJ45XrO0MTxxyyMHKb2dBS-DTqlrMDZZi9I4-89h_gB9UtB7</recordid><startdate>201301</startdate><enddate>201301</enddate><creator>Portsmouth, Simon</creator><creator>Valluri, Srinivas Rao</creator><creator>Däumer, Martin</creator><creator>Thiele, Bernhard</creator><creator>Valdez, Hernan</creator><creator>Lewis, Marilyn</creator><creator>Craig, Charles</creator><creator>Thielen, Alexander</creator><creator>James, Ian</creator><creator>Demarest, James</creator><creator>Heera, Jayvant</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><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>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201301</creationdate><title>Correlation between genotypic (V3 population sequencing) and phenotypic (Trofile ES) methods of characterizing co-receptor usage of HIV-1 from 200 treatment-naïve HIV patients screened for Study A4001078</title><author>Portsmouth, Simon ; Valluri, Srinivas Rao ; Däumer, Martin ; Thiele, Bernhard ; Valdez, Hernan ; Lewis, Marilyn ; Craig, Charles ; Thielen, Alexander ; James, Ian ; Demarest, James ; Heera, Jayvant</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-17b644b627a0e351668a622751bd922f5680d95b3537f38d24da4e37a1bafd6e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Algorithms</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Clinical trials</topic><topic>CXCR5</topic><topic>Data processing</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>Genotyping</topic><topic>High-Throughput Nucleotide Sequencing - methods</topic><topic>HIV Infections - virology</topic><topic>HIV-1</topic><topic>HIV-1 - genetics</topic><topic>HIV-1 - isolation & purification</topic><topic>HIV-1 - physiology</topic><topic>Human immunodeficiency virus 1</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunodeficiencies</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Infectious diseases</topic><topic>Maraviroc</topic><topic>Medical sciences</topic><topic>Pharmacology. 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Assessment of HIV-1 co-receptor usage is essential to identify patients who are likely to respond to maraviroc (MVC)-containing regimens. Co-receptor usage of plasma virus from all treatment-naïve patients screened for a MVC clinical trial was assessed using phenotypic and genotypic methodologies to evaluate concordance between testing methods and to assess the quantity of CXCR4-using (non-R5) virus in samples giving discordant results. Co-receptor usage was prospectively measured using the enhanced sensitivity Trofile assay (Trofile ES) to screen patients for enrollment in Study A4001078. Population and deep sequencing methodologies were utilized retrospectively to analyze all screening samples, with co-receptor usage determined using the geno2pheno algorithm. Concordance between methods was explored using descriptive statistics. The quantity of non-R5 virus in all samples was measured using deep sequencing. Trofile ES and matched genotype results were obtained for 199screening samples. Concordance of Trofile ES with population genotyping (5.75% false-positive rate [FPR]) and deep sequencing (3.5% FPR; 2% non-R5 threshold) was 91.7% and 89.6%, respectively. Population genotype data were available for all samples with non-reportable Trofile ES results; the distribution of co-receptor usage in this set was consistent with that in the overall population: 75% (12/16) R5 and 25% (4/16) non-R5. The majority of samples contained non-R5 plasma HIV-1 RNA estimated at either <1 log10 (62.0%) or ⩾4 log10 (30.5%) copies/mL; the absolute amount of detectable non-R5 virus remained stable between screening and baseline visits. Samples originally classified as non-R5 by Trofile ES but R5 by population sequencing had a relatively low absolute amount of non-R5 virus (mean 2.1%, median 0.1%). The determination of co-receptor usage using either Trofile ES or genotyping methodologies showed similar frequencies of R5 and non-R5 virus in this treatment-naïve study population. For both concordant and discordant samples, population sequencing appropriately identified R5 samples with low levels of non-R5-using virus.</abstract><cop>Kidlington</cop><pub>Elsevier B.V</pub><pmid>23165088</pmid><doi>10.1016/j.antiviral.2012.11.002</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Antiviral research, 2013-01, Vol.97 (1), p.60-65 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Algorithms Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Clinical trials CXCR5 Data processing Genotype Genotypes Genotyping High-Throughput Nucleotide Sequencing - methods HIV Infections - virology HIV-1 HIV-1 - genetics HIV-1 - isolation & purification HIV-1 - physiology Human immunodeficiency virus 1 Human viral diseases Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Infectious diseases Maraviroc Medical sciences Pharmacology. Drug treatments Phenotype Population studies Prospective Studies Receptors, HIV - analysis RNA RNA, Viral - genetics Statistics Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Virology - methods Virus Attachment |
| title | Correlation between genotypic (V3 population sequencing) and phenotypic (Trofile ES) methods of characterizing co-receptor usage of HIV-1 from 200 treatment-naïve HIV patients screened for Study A4001078 |
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