Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease
Abstract Objectives To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options. Methods HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) valu...
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| Veröffentlicht in: | Journal of antimicrobial chemotherapy 2021-11, Vol.76 (12), p.3272-3279 |
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| creator | Bouba, Yagai Armenia, Daniele Forbici, Federica Bertoli, Ada Borghi, Vanni Gagliardini, Roberta Vergori, Alessandra Cicalini, Stefania Mazzotta, Valentina Malagnino, Vincenzo Lichtner, Miriam Latini, Alessandra Mussini, Cristina Andreoni, Massimo Antinori, Andrea Perno, Carlo Federico Ceccherini-Silberstein, Francesca Santoro, Maria Mercedes |
| description | Abstract
Objectives
To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options.
Methods
HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm.
Results
Overall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33–211) and 312 (155–517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%–10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count |
| doi_str_mv | 10.1093/jac/dkab322 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2574405095</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/jac/dkab322</oup_id><sourcerecordid>2574405095</sourcerecordid><originalsourceid>FETCH-LOGICAL-c315t-5a83e8007e54bc6edf76a70d7b4402b9f1ac31afa4f2bb307973e7f049aeaa3d3</originalsourceid><addsrcrecordid>eNp9kE1LxDAQQIMoun6cvEtOIkh12jTN9ijiFwhe1GuZNlM32jaxSdX990Z29ehpDvPmwTzGDlM4S6EU56_YnOs3rEWWbbBZmheQZFCmm2wGAmSicil22K73rwBQyGK-zXZELrNSlWrGljc02LB0puG3d89JysNonfE91xRo7M2AwdiB9-ZlEfiCOseD5UbTEEy75I6s64h_mrDg9LXAyQfSUUEY-ohw636uPcdBc9QfODRxrY0n9LTPtlrsPB2s5x57ur56vLxN7h9u7i4v7pNGpDIkEueC5gCKZF43BelWFahAqzrPIavLNsUIYot5m9W1gPiVINVCXiIhCi322MnK60b7PpEPVW98Q12HA9nJV5lU0SShlBE9XaHNaL0fqa3caHocl1UK1U_rKrau1q0jfbQWT3VP-o_9jRuB4xVgJ_ev6Rts04rW</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2574405095</pqid></control><display><type>article</type><title>Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Bouba, Yagai ; Armenia, Daniele ; Forbici, Federica ; Bertoli, Ada ; Borghi, Vanni ; Gagliardini, Roberta ; Vergori, Alessandra ; Cicalini, Stefania ; Mazzotta, Valentina ; Malagnino, Vincenzo ; Lichtner, Miriam ; Latini, Alessandra ; Mussini, Cristina ; Andreoni, Massimo ; Antinori, Andrea ; Perno, Carlo Federico ; Ceccherini-Silberstein, Francesca ; Santoro, Maria Mercedes</creator><creatorcontrib>Bouba, Yagai ; Armenia, Daniele ; Forbici, Federica ; Bertoli, Ada ; Borghi, Vanni ; Gagliardini, Roberta ; Vergori, Alessandra ; Cicalini, Stefania ; Mazzotta, Valentina ; Malagnino, Vincenzo ; Lichtner, Miriam ; Latini, Alessandra ; Mussini, Cristina ; Andreoni, Massimo ; Antinori, Andrea ; Perno, Carlo Federico ; Ceccherini-Silberstein, Francesca ; Santoro, Maria Mercedes</creatorcontrib><description>Abstract
Objectives
To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options.
Methods
HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm.
Results
Overall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33–211) and 312 (155–517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%–10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count <200 cells/mm3, who were perinatally infected and with a long treatment history significantly increased as FPR levels decreased. Regarding resistance, 933 (67.5%) individuals accumulated at least one class resistance, with 52.7%, 48.2%, 23.5% and 13.2% of individuals showing resistance to NRTIs, NNRTIs, PIs and INIs; while 23.2%, 27.2%, 14.3% and 2.8% harboured resistance to 1, 2, 3 and 4 classes, respectively. Individuals with FPR ≤5% showed a significantly higher level of resistance to PIs, NRTIs and INIs compared with others. The proportion of individuals harbouring strains susceptible to ≤2 active drugs was only about 2%; nonetheless, this proportion doubled (4.6%) in patients infected with FPR ≤5%.
Conclusions
Our findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkab322</identifier><identifier>PMID: 34529797</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>CD4 Lymphocyte Count ; Genotype ; HIV Infections - drug therapy ; HIV-1 - genetics ; Humans ; Tropism ; Viral Load ; Viral Tropism</subject><ispartof>Journal of antimicrobial chemotherapy, 2021-11, Vol.76 (12), p.3272-3279</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c315t-5a83e8007e54bc6edf76a70d7b4402b9f1ac31afa4f2bb307973e7f049aeaa3d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34529797$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bouba, Yagai</creatorcontrib><creatorcontrib>Armenia, Daniele</creatorcontrib><creatorcontrib>Forbici, Federica</creatorcontrib><creatorcontrib>Bertoli, Ada</creatorcontrib><creatorcontrib>Borghi, Vanni</creatorcontrib><creatorcontrib>Gagliardini, Roberta</creatorcontrib><creatorcontrib>Vergori, Alessandra</creatorcontrib><creatorcontrib>Cicalini, Stefania</creatorcontrib><creatorcontrib>Mazzotta, Valentina</creatorcontrib><creatorcontrib>Malagnino, Vincenzo</creatorcontrib><creatorcontrib>Lichtner, Miriam</creatorcontrib><creatorcontrib>Latini, Alessandra</creatorcontrib><creatorcontrib>Mussini, Cristina</creatorcontrib><creatorcontrib>Andreoni, Massimo</creatorcontrib><creatorcontrib>Antinori, Andrea</creatorcontrib><creatorcontrib>Perno, Carlo Federico</creatorcontrib><creatorcontrib>Ceccherini-Silberstein, Francesca</creatorcontrib><creatorcontrib>Santoro, Maria Mercedes</creatorcontrib><title>Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Abstract
Objectives
To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options.
Methods
HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm.
Results
Overall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33–211) and 312 (155–517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%–10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count <200 cells/mm3, who were perinatally infected and with a long treatment history significantly increased as FPR levels decreased. Regarding resistance, 933 (67.5%) individuals accumulated at least one class resistance, with 52.7%, 48.2%, 23.5% and 13.2% of individuals showing resistance to NRTIs, NNRTIs, PIs and INIs; while 23.2%, 27.2%, 14.3% and 2.8% harboured resistance to 1, 2, 3 and 4 classes, respectively. Individuals with FPR ≤5% showed a significantly higher level of resistance to PIs, NRTIs and INIs compared with others. The proportion of individuals harbouring strains susceptible to ≤2 active drugs was only about 2%; nonetheless, this proportion doubled (4.6%) in patients infected with FPR ≤5%.
Conclusions
Our findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease.</description><subject>CD4 Lymphocyte Count</subject><subject>Genotype</subject><subject>HIV Infections - drug therapy</subject><subject>HIV-1 - genetics</subject><subject>Humans</subject><subject>Tropism</subject><subject>Viral Load</subject><subject>Viral Tropism</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQQIMoun6cvEtOIkh12jTN9ijiFwhe1GuZNlM32jaxSdX990Z29ehpDvPmwTzGDlM4S6EU56_YnOs3rEWWbbBZmheQZFCmm2wGAmSicil22K73rwBQyGK-zXZELrNSlWrGljc02LB0puG3d89JysNonfE91xRo7M2AwdiB9-ZlEfiCOseD5UbTEEy75I6s64h_mrDg9LXAyQfSUUEY-ohw636uPcdBc9QfODRxrY0n9LTPtlrsPB2s5x57ur56vLxN7h9u7i4v7pNGpDIkEueC5gCKZF43BelWFahAqzrPIavLNsUIYot5m9W1gPiVINVCXiIhCi322MnK60b7PpEPVW98Q12HA9nJV5lU0SShlBE9XaHNaL0fqa3caHocl1UK1U_rKrau1q0jfbQWT3VP-o_9jRuB4xVgJ_ev6Rts04rW</recordid><startdate>20211112</startdate><enddate>20211112</enddate><creator>Bouba, Yagai</creator><creator>Armenia, Daniele</creator><creator>Forbici, Federica</creator><creator>Bertoli, Ada</creator><creator>Borghi, Vanni</creator><creator>Gagliardini, Roberta</creator><creator>Vergori, Alessandra</creator><creator>Cicalini, Stefania</creator><creator>Mazzotta, Valentina</creator><creator>Malagnino, Vincenzo</creator><creator>Lichtner, Miriam</creator><creator>Latini, Alessandra</creator><creator>Mussini, Cristina</creator><creator>Andreoni, Massimo</creator><creator>Antinori, Andrea</creator><creator>Perno, Carlo Federico</creator><creator>Ceccherini-Silberstein, Francesca</creator><creator>Santoro, Maria Mercedes</creator><general>Oxford University Press</general><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></search><sort><creationdate>20211112</creationdate><title>Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease</title><author>Bouba, Yagai ; Armenia, Daniele ; Forbici, Federica ; Bertoli, Ada ; Borghi, Vanni ; Gagliardini, Roberta ; Vergori, Alessandra ; Cicalini, Stefania ; Mazzotta, Valentina ; Malagnino, Vincenzo ; Lichtner, Miriam ; Latini, Alessandra ; Mussini, Cristina ; Andreoni, Massimo ; Antinori, Andrea ; Perno, Carlo Federico ; Ceccherini-Silberstein, Francesca ; Santoro, Maria Mercedes</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c315t-5a83e8007e54bc6edf76a70d7b4402b9f1ac31afa4f2bb307973e7f049aeaa3d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>CD4 Lymphocyte Count</topic><topic>Genotype</topic><topic>HIV Infections - drug therapy</topic><topic>HIV-1 - genetics</topic><topic>Humans</topic><topic>Tropism</topic><topic>Viral Load</topic><topic>Viral Tropism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bouba, Yagai</creatorcontrib><creatorcontrib>Armenia, Daniele</creatorcontrib><creatorcontrib>Forbici, Federica</creatorcontrib><creatorcontrib>Bertoli, Ada</creatorcontrib><creatorcontrib>Borghi, Vanni</creatorcontrib><creatorcontrib>Gagliardini, Roberta</creatorcontrib><creatorcontrib>Vergori, Alessandra</creatorcontrib><creatorcontrib>Cicalini, Stefania</creatorcontrib><creatorcontrib>Mazzotta, Valentina</creatorcontrib><creatorcontrib>Malagnino, Vincenzo</creatorcontrib><creatorcontrib>Lichtner, Miriam</creatorcontrib><creatorcontrib>Latini, Alessandra</creatorcontrib><creatorcontrib>Mussini, Cristina</creatorcontrib><creatorcontrib>Andreoni, Massimo</creatorcontrib><creatorcontrib>Antinori, Andrea</creatorcontrib><creatorcontrib>Perno, Carlo Federico</creatorcontrib><creatorcontrib>Ceccherini-Silberstein, Francesca</creatorcontrib><creatorcontrib>Santoro, Maria Mercedes</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of antimicrobial chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bouba, Yagai</au><au>Armenia, Daniele</au><au>Forbici, Federica</au><au>Bertoli, Ada</au><au>Borghi, Vanni</au><au>Gagliardini, Roberta</au><au>Vergori, Alessandra</au><au>Cicalini, Stefania</au><au>Mazzotta, Valentina</au><au>Malagnino, Vincenzo</au><au>Lichtner, Miriam</au><au>Latini, Alessandra</au><au>Mussini, Cristina</au><au>Andreoni, Massimo</au><au>Antinori, Andrea</au><au>Perno, Carlo Federico</au><au>Ceccherini-Silberstein, Francesca</au><au>Santoro, Maria Mercedes</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2021-11-12</date><risdate>2021</risdate><volume>76</volume><issue>12</issue><spage>3272</spage><epage>3279</epage><pages>3272-3279</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><abstract>Abstract
Objectives
To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options.
Methods
HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm.
Results
Overall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33–211) and 312 (155–517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%–10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count <200 cells/mm3, who were perinatally infected and with a long treatment history significantly increased as FPR levels decreased. Regarding resistance, 933 (67.5%) individuals accumulated at least one class resistance, with 52.7%, 48.2%, 23.5% and 13.2% of individuals showing resistance to NRTIs, NNRTIs, PIs and INIs; while 23.2%, 27.2%, 14.3% and 2.8% harboured resistance to 1, 2, 3 and 4 classes, respectively. Individuals with FPR ≤5% showed a significantly higher level of resistance to PIs, NRTIs and INIs compared with others. The proportion of individuals harbouring strains susceptible to ≤2 active drugs was only about 2%; nonetheless, this proportion doubled (4.6%) in patients infected with FPR ≤5%.
Conclusions
Our findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>34529797</pmid><doi>10.1093/jac/dkab322</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | CD4 Lymphocyte Count Genotype HIV Infections - drug therapy HIV-1 - genetics Humans Tropism Viral Load Viral Tropism |
| title | Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease |
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