Publicação
Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-native individuals
| Resumo: | Background: INSTIs have become a pillar of first-line ART. Real-world data are needed to assess their effectiveness in routine care. Objectives: We analysed ART-naive patients who started INSTI-based regimens in 2012-19 whose data were collected by INTEGRATE, a European collaborative study including seven national cohorts. Methods: Kaplan-Meier analyses assessed time to virological failure (VF), defined as one viral load (VL) ≥1000 copies/mL, two consecutive VLs ≥50 copies/mL, or one VL ≥50 copies/mL followed by treatment change after ≥24 weeks of follow-up, and time to INSTIs discontinuation (INSTI-DC) for any reason. Factors associated with VF and INSTI-DC were explored by logistic regression analysis. Results: Of 2976 regimens started, 1901 (63.9%) contained dolutegravir, 631 (21.2%) elvitegravir and 444 (14.9%) raltegravir. The 1 year estimated probabilities of VF and INSTI-DC were 5.6% (95% CI 4.5-6.7) and 16.2% (95% CI 14.9-17.6), respectively, and were higher for raltegravir versus both elvitegravir and dolutegravir. A baseline VL ≥100 000 copies/mL [adjusted HR (aHR) 2.17, 95% CI 1.55-3.04, P < 0.001] increased the risk of VF, while a pre-treatment CD4 count ≥200 cells/mm3 reduced the risk (aHR 0.52, 95% CI 0.37-0.74, P < 0.001). Predictors of INSTI-DC included use of raltegravir versus dolutegravir (aHR 3.03, 95% CI 2.34-3.92, P < 0.001), use of >3 drugs versus 3 drugs (aHR 2.73, 95% CI 1.55-4.79, P < 0.001) and starting ART following availability of dolutegravir (aHR 0.64, 95% CI 0.48-0.83, P = 0.001). Major INSTI mutations indicative of transmitted drug resistance occurred in 2/1114 (0.2%) individuals. Conclusions: This large multi-cohort study indicates high effectiveness of elvitegravir- or dolutegravir-based first-line ART in routine practice across Europe. |
|---|---|
| Autores principais: | Rossetti, Barbara |
| Outros Autores: | Fabbiani, Massimiliano; Di Carlo, Domenico; Incardona, F.; Abecasis, A.; Gomes, Perpetua; Geretti, A. M.; Seguin-Devaux, C.; Garcia, Federico; Kaiser, Rolf; Modica, Sara; Shallvari, Adrian; Sönnerborg, A.; Zazzi, M.; Bobkova, M.; Seguin-Devaux, C.; Paredes, R.; Sayan, M.; Vandamme, A. M. |
| Assunto: | Pharmacology Microbiology (medical) Infectious Diseases Pharmacology (medical) SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure SDG 12 - Responsible Consumption and Production |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1868983452645195776 |
|---|---|
| author | Rossetti, Barbara |
| author2 | Fabbiani, Massimiliano Di Carlo, Domenico Incardona, F. Abecasis, A. Gomes, Perpetua Geretti, A. M. Seguin-Devaux, C. Garcia, Federico Kaiser, Rolf Modica, Sara Shallvari, Adrian Sönnerborg, A. Zazzi, M. Bobkova, M. Seguin-Devaux, C. Paredes, R. Sayan, M. Vandamme, A. M. |
| author2_role | author author author author author author author author author author author author author author author author author author |
| author_facet | Rossetti, Barbara Fabbiani, Massimiliano Di Carlo, Domenico Incardona, F. Abecasis, A. Gomes, Perpetua Geretti, A. M. Seguin-Devaux, C. Garcia, Federico Kaiser, Rolf Modica, Sara Shallvari, Adrian Sönnerborg, A. Zazzi, M. Bobkova, M. Seguin-Devaux, C. Paredes, R. Sayan, M. Vandamme, A. M. |
| author_role | author |
| contributor_name_str_mv | TB, HIV and opportunistic diseases and pathogens (THOP) Global Health and Tropical Medicine (GHTM) Instituto de Higiene e Medicina Tropical (IHMT) British Society for Antimicrobial Chemotherapy | Oxford University Press RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Rossetti, Barbara\"},{\"Person.name\":\"Fabbiani, Massimiliano\"},{\"Person.name\":\"Di Carlo, Domenico\"},{\"Person.name\":\"Incardona, F.\"},{\"Person.name\":\"Abecasis, A.\"},{\"Person.name\":\"Gomes, Perpetua\"},{\"Person.name\":\"Geretti, A. M.\"},{\"Person.name\":\"Seguin-Devaux, C.\"},{\"Person.name\":\"Garcia, Federico\"},{\"Person.name\":\"Kaiser, Rolf\"},{\"Person.name\":\"Modica, Sara\"},{\"Person.name\":\"Shallvari, Adrian\"},{\"Person.name\":\"Sönnerborg, A.\"},{\"Person.name\":\"Zazzi, M.\"},{\"Person.name\":\"Bobkova, M.\"},{\"Person.name\":\"Seguin-Devaux, C.\"},{\"Person.name\":\"Paredes, R.\"},{\"Person.name\":\"Sayan, M.\"},{\"Person.name\":\"Vandamme, A. M.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | TB, HIV and opportunistic diseases and pathogens (THOP) Global Health and Tropical Medicine (GHTM) Instituto de Higiene e Medicina Tropical (IHMT) British Society for Antimicrobial Chemotherapy | Oxford University Press RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Rossetti, Barbara Fabbiani, Massimiliano Di Carlo, Domenico Incardona, F. Abecasis, A. Gomes, Perpetua Geretti, A. M. Seguin-Devaux, C. Garcia, Federico Kaiser, Rolf Modica, Sara Shallvari, Adrian Sönnerborg, A. Zazzi, M. Bobkova, M. Seguin-Devaux, C. Paredes, R. Sayan, M. Vandamme, A. M. |
| datacite.date.Accepted.fl_str_mv | 2021-09-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2021-09-24T02:25:09Z |
| datacite.date.embargoed.fl_str_mv | 2021-09-24T02:25:09Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Pharmacology Microbiology (medical) Infectious Diseases Pharmacology (medical) SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure SDG 12 - Responsible Consumption and Production |
| datacite.titles.title.fl_str_mv | Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-native individuals Results from a European multi-cohort study |
| dc.contributor.none.fl_str_mv | TB, HIV and opportunistic diseases and pathogens (THOP) Global Health and Tropical Medicine (GHTM) Instituto de Higiene e Medicina Tropical (IHMT) British Society for Antimicrobial Chemotherapy | Oxford University Press RUN |
| dc.creator.none.fl_str_mv | Rossetti, Barbara Fabbiani, Massimiliano Di Carlo, Domenico Incardona, F. Abecasis, A. Gomes, Perpetua Geretti, A. M. Seguin-Devaux, C. Garcia, Federico Kaiser, Rolf Modica, Sara Shallvari, Adrian Sönnerborg, A. Zazzi, M. Bobkova, M. Seguin-Devaux, C. Paredes, R. Sayan, M. Vandamme, A. M. |
| dc.date.Accepted.fl_str_mv | 2021-09-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2021-09-24T02:25:09Z |
| dc.date.embargoed.fl_str_mv | 2021-09-24T02:25:09Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/125098 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Pharmacology Microbiology (medical) Infectious Diseases Pharmacology (medical) SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure SDG 12 - Responsible Consumption and Production |
| dc.title.fl_str_mv | Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-native individuals Results from a European multi-cohort study |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Background: INSTIs have become a pillar of first-line ART. Real-world data are needed to assess their effectiveness in routine care. Objectives: We analysed ART-naive patients who started INSTI-based regimens in 2012-19 whose data were collected by INTEGRATE, a European collaborative study including seven national cohorts. Methods: Kaplan-Meier analyses assessed time to virological failure (VF), defined as one viral load (VL) ≥1000 copies/mL, two consecutive VLs ≥50 copies/mL, or one VL ≥50 copies/mL followed by treatment change after ≥24 weeks of follow-up, and time to INSTIs discontinuation (INSTI-DC) for any reason. Factors associated with VF and INSTI-DC were explored by logistic regression analysis. Results: Of 2976 regimens started, 1901 (63.9%) contained dolutegravir, 631 (21.2%) elvitegravir and 444 (14.9%) raltegravir. The 1 year estimated probabilities of VF and INSTI-DC were 5.6% (95% CI 4.5-6.7) and 16.2% (95% CI 14.9-17.6), respectively, and were higher for raltegravir versus both elvitegravir and dolutegravir. A baseline VL ≥100 000 copies/mL [adjusted HR (aHR) 2.17, 95% CI 1.55-3.04, P < 0.001] increased the risk of VF, while a pre-treatment CD4 count ≥200 cells/mm3 reduced the risk (aHR 0.52, 95% CI 0.37-0.74, P < 0.001). Predictors of INSTI-DC included use of raltegravir versus dolutegravir (aHR 3.03, 95% CI 2.34-3.92, P < 0.001), use of >3 drugs versus 3 drugs (aHR 2.73, 95% CI 1.55-4.79, P < 0.001) and starting ART following availability of dolutegravir (aHR 0.64, 95% CI 0.48-0.83, P = 0.001). Major INSTI mutations indicative of transmitted drug resistance occurred in 2/1114 (0.2%) individuals. Conclusions: This large multi-cohort study indicates high effectiveness of elvitegravir- or dolutegravir-based first-line ART in routine practice across Europe. |
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| eu_rights_str_mv | openAccess |
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| identifier.url.fl_str_mv | http://hdl.handle.net/10362/125098 |
| inst_facet_str | urn:organizationAcronym:unl{{{_:::_}}}Universidade Nova de Lisboa |
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| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
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| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/125098 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Rossetti, Barbara Fabbiani, Massimiliano Di Carlo, Domenico Incardona, F. Abecasis, A. Gomes, Perpetua Geretti, A. M. Seguin-Devaux, C. Garcia, Federico Kaiser, Rolf Modica, Sara Shallvari, Adrian Sönnerborg, A. Zazzi, M. Bobkova, M. Seguin-Devaux, C. Paredes, R. Sayan, M. Vandamme, A. M. |
| publishDate | 2021 |
| repo_facet_str | urn:repositoryAcronym:run{{{_:::_}}}Repositório Institucional da UNL |
| reponame_str | Repositório Institucional da UNL |
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| spelling | engenBackground: INSTIs have become a pillar of first-line ART. Real-world data are needed to assess their effectiveness in routine care. Objectives: We analysed ART-naive patients who started INSTI-based regimens in 2012-19 whose data were collected by INTEGRATE, a European collaborative study including seven national cohorts. Methods: Kaplan-Meier analyses assessed time to virological failure (VF), defined as one viral load (VL) ≥1000 copies/mL, two consecutive VLs ≥50 copies/mL, or one VL ≥50 copies/mL followed by treatment change after ≥24 weeks of follow-up, and time to INSTIs discontinuation (INSTI-DC) for any reason. Factors associated with VF and INSTI-DC were explored by logistic regression analysis. Results: Of 2976 regimens started, 1901 (63.9%) contained dolutegravir, 631 (21.2%) elvitegravir and 444 (14.9%) raltegravir. The 1 year estimated probabilities of VF and INSTI-DC were 5.6% (95% CI 4.5-6.7) and 16.2% (95% CI 14.9-17.6), respectively, and were higher for raltegravir versus both elvitegravir and dolutegravir. A baseline VL ≥100 000 copies/mL [adjusted HR (aHR) 2.17, 95% CI 1.55-3.04, P < 0.001] increased the risk of VF, while a pre-treatment CD4 count ≥200 cells/mm3 reduced the risk (aHR 0.52, 95% CI 0.37-0.74, P < 0.001). Predictors of INSTI-DC included use of raltegravir versus dolutegravir (aHR 3.03, 95% CI 2.34-3.92, P < 0.001), use of >3 drugs versus 3 drugs (aHR 2.73, 95% CI 1.55-4.79, P < 0.001) and starting ART following availability of dolutegravir (aHR 0.64, 95% CI 0.48-0.83, P = 0.001). Major INSTI mutations indicative of transmitted drug resistance occurred in 2/1114 (0.2%) individuals. Conclusions: This large multi-cohort study indicates high effectiveness of elvitegravir- or dolutegravir-based first-line ART in routine practice across Europe.application/pdfenEffectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-native individualsSubtitleenResults from a European multi-cohort studyRossetti, BarbaraFabbiani, MassimilianoDi Carlo, DomenicoIncardona, F.Abecasis, A.Gomes, PerpetuaGeretti, A. M.Seguin-Devaux, C.Garcia, FedericoKaiser, RolfModica, SaraShallvari, AdrianSönnerborg, A.Zazzi, M.Bobkova, M.Seguin-Devaux, C.Paredes, R.Sayan, M.Vandamme, A. M.TB, HIV and opportunistic diseases and pathogens (THOP)Global Health and Tropical Medicine (GHTM)Instituto de Higiene e Medicina Tropical (IHMT)British Society for Antimicrobial Chemotherapy | Oxford University PressHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf0305-7453URNIsPartOfPURE: 33793803URNIsPartOfPURE UUID: 3024eecf-813b-42f6-9c2f-1fb43428c297URNIsPartOfScopus: 85114380094URNIsPartOfPubMed: 34212176DOIIsPartOf10.1093/jac/dkab2002021-09-24T02:25:09Z2021-09-012021-09-01T00:00:00ZHandlehttp://hdl.handle.net/10362/125098http://purl.org/coar/access_right/c_abf2open accessPharmacologyMicrobiology (medical)Infectious DiseasesPharmacology (medical)SDG 3 - Good Health and Well-beingSDG 9 - Industry, Innovation, and InfrastructureSDG 12 - Responsible Consumption and Production338044 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/ca8dfd69-ad7d-44f3-a317-a54a8bb41fc2/download |
| spellingShingle | Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-native individuals Rossetti, Barbara Pharmacology Microbiology (medical) Infectious Diseases Pharmacology (medical) SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure SDG 12 - Responsible Consumption and Production |
| status | SINGLETON |
| subject.fl_str_mv | Pharmacology Microbiology (medical) Infectious Diseases Pharmacology (medical) SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure SDG 12 - Responsible Consumption and Production |
| title | Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-native individuals |
| title_full | Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-native individuals |
| title_fullStr | Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-native individuals |
| title_full_unstemmed | Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-native individuals |
| title_short | Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-native individuals |
| title_sort | Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-native individuals |
| topic | Pharmacology Microbiology (medical) Infectious Diseases Pharmacology (medical) SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure SDG 12 - Responsible Consumption and Production |
| topic_facet | Pharmacology Microbiology (medical) Infectious Diseases Pharmacology (medical) SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure SDG 12 - Responsible Consumption and Production |
| url | http://hdl.handle.net/10362/125098 |
| visible | 1 |