Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients
The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir). Dat...
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| creator | Fourati, Slim Charpentier, Charlotte Amiel, Corinne Morand-Joubert, Laurence Reigadas, Sandrine Trabaud, Mary-Anne Delaugerre, Constance Nicot, Florence Rodallec, Audrey Maillard, Anne Mirand, Audrey Jeulin, Hélène Montès, Brigitte Barin, Francis Bettinger, Dominique Le Guillou-Guillemette, Hélène Vallet, Sophie Signori-Schmuck, Anne Descamps, Diane Calvez, Vincent Flandre, Philippe Marcelin, Anne-Genevieve |
| description | The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir).
Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23).
Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P |
| doi_str_mv | 10.1093/jac/dku535 |
| format | Article |
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Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23).
Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P < 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P < 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes (P = 0.004).
This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dku535</identifier><identifier>PMID: 25558077</identifier><language>eng</language><publisher>England: Oxford Publishing Limited (England)</publisher><subject>Adult ; Anti-HIV Agents - pharmacology ; Anti-HIV Agents - therapeutic use ; Antiretroviral drugs ; Drug resistance ; Drug Resistance, Viral ; Drug therapy ; Female ; France ; Heterocyclic Compounds, 3-Ring - pharmacology ; HIV ; HIV Infections - drug therapy ; HIV Infections - virology ; HIV Integrase - genetics ; HIV Protease - genetics ; HIV Reverse Transcriptase - genetics ; HIV-1 - drug effects ; HIV-1 - enzymology ; HIV-1 - genetics ; Human immunodeficiency virus ; Humans ; Life Sciences ; Male ; Middle Aged ; Mutant Proteins - genetics ; Mutation ; Patients ; Quinolones - pharmacology ; Raltegravir Potassium - therapeutic use ; Sequence Analysis, DNA</subject><ispartof>Journal of antimicrobial chemotherapy, 2015-05, Vol.70 (5), p.1507-1512</ispartof><rights>The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</rights><rights>Copyright Oxford Publishing Limited(England) May 2015</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c315t-e357ea0b2560c99b018e7ae38d733c4f58973f944e5f7e4b28d264f77cc1dbc83</citedby><cites>FETCH-LOGICAL-c315t-e357ea0b2560c99b018e7ae38d733c4f58973f944e5f7e4b28d264f77cc1dbc83</cites><orcidid>0000-0002-2612-3522 ; 0000-0003-4808-8999 ; 0000-0001-6861-236X ; 0000-0003-4348-4247 ; 0000-0001-8614-1071 ; 0009-0002-6855-3472 ; 0000-0003-2866-4274 ; 0009-0002-7269-2328</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25558077$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01392320$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Fourati, Slim</creatorcontrib><creatorcontrib>Charpentier, Charlotte</creatorcontrib><creatorcontrib>Amiel, Corinne</creatorcontrib><creatorcontrib>Morand-Joubert, Laurence</creatorcontrib><creatorcontrib>Reigadas, Sandrine</creatorcontrib><creatorcontrib>Trabaud, Mary-Anne</creatorcontrib><creatorcontrib>Delaugerre, Constance</creatorcontrib><creatorcontrib>Nicot, Florence</creatorcontrib><creatorcontrib>Rodallec, Audrey</creatorcontrib><creatorcontrib>Maillard, Anne</creatorcontrib><creatorcontrib>Mirand, Audrey</creatorcontrib><creatorcontrib>Jeulin, Hélène</creatorcontrib><creatorcontrib>Montès, Brigitte</creatorcontrib><creatorcontrib>Barin, Francis</creatorcontrib><creatorcontrib>Bettinger, Dominique</creatorcontrib><creatorcontrib>Le Guillou-Guillemette, Hélène</creatorcontrib><creatorcontrib>Vallet, Sophie</creatorcontrib><creatorcontrib>Signori-Schmuck, Anne</creatorcontrib><creatorcontrib>Descamps, Diane</creatorcontrib><creatorcontrib>Calvez, Vincent</creatorcontrib><creatorcontrib>Flandre, Philippe</creatorcontrib><creatorcontrib>Marcelin, Anne-Genevieve</creatorcontrib><creatorcontrib>ANRS AC11 Resistance Study Group</creatorcontrib><creatorcontrib>on behalf of the ANRS AC11 Resistance Study Group</creatorcontrib><title>Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir).
Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23).
Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P < 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P < 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes (P = 0.004).
This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen.</description><subject>Adult</subject><subject>Anti-HIV Agents - pharmacology</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretroviral drugs</subject><subject>Drug resistance</subject><subject>Drug Resistance, Viral</subject><subject>Drug therapy</subject><subject>Female</subject><subject>France</subject><subject>Heterocyclic Compounds, 3-Ring - pharmacology</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - virology</subject><subject>HIV Integrase - genetics</subject><subject>HIV Protease - genetics</subject><subject>HIV Reverse Transcriptase - genetics</subject><subject>HIV-1 - drug effects</subject><subject>HIV-1 - enzymology</subject><subject>HIV-1 - genetics</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutant Proteins - 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Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23).
Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P < 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P < 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes (P = 0.004).
This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen.</abstract><cop>England</cop><pub>Oxford Publishing Limited (England)</pub><pmid>25558077</pmid><doi>10.1093/jac/dku535</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-2612-3522</orcidid><orcidid>https://orcid.org/0000-0003-4808-8999</orcidid><orcidid>https://orcid.org/0000-0001-6861-236X</orcidid><orcidid>https://orcid.org/0000-0003-4348-4247</orcidid><orcidid>https://orcid.org/0000-0001-8614-1071</orcidid><orcidid>https://orcid.org/0009-0002-6855-3472</orcidid><orcidid>https://orcid.org/0000-0003-2866-4274</orcidid><orcidid>https://orcid.org/0009-0002-7269-2328</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0305-7453 |
| ispartof | Journal of antimicrobial chemotherapy, 2015-05, Vol.70 (5), p.1507-1512 |
| issn | 0305-7453 1460-2091 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_01392320v1 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adult Anti-HIV Agents - pharmacology Anti-HIV Agents - therapeutic use Antiretroviral drugs Drug resistance Drug Resistance, Viral Drug therapy Female France Heterocyclic Compounds, 3-Ring - pharmacology HIV HIV Infections - drug therapy HIV Infections - virology HIV Integrase - genetics HIV Protease - genetics HIV Reverse Transcriptase - genetics HIV-1 - drug effects HIV-1 - enzymology HIV-1 - genetics Human immunodeficiency virus Humans Life Sciences Male Middle Aged Mutant Proteins - genetics Mutation Patients Quinolones - pharmacology Raltegravir Potassium - therapeutic use Sequence Analysis, DNA |
| title | Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T13%3A27%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cross-resistance%20to%20elvitegravir%20and%20dolutegravir%20in%20502%20patients%20failing%20on%20raltegravir:%20a%20French%20national%20study%20of%20raltegravir-experienced%20HIV-1-infected%20patients&rft.jtitle=Journal%20of%20antimicrobial%20chemotherapy&rft.au=Fourati,%20Slim&rft.aucorp=ANRS%20AC11%20Resistance%20Study%20Group&rft.date=2015-05-01&rft.volume=70&rft.issue=5&rft.spage=1507&rft.epage=1512&rft.pages=1507-1512&rft.issn=0305-7453&rft.eissn=1460-2091&rft_id=info:doi/10.1093/jac/dku535&rft_dat=%3Cproquest_hal_p%3E3666832311%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1675996863&rft_id=info:pmid/25558077&rfr_iscdi=true |