Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study
Background: Over the past decade, antiretroviral therapy (ART) regimens that include integrase strand inhibitors (INSTIs) have become the most commonly used for people with HIV starting ART. Although trials and observational studies have compared virological failure on INSTI-based with other regimen...
| Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | article |
| Status: | Published version |
| Publication Date: | 2022 |
| Country: | España |
| Institution: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repository: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p15819 |
| Online Access: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15819 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85131364296&doi=10.1016%2fS2352-3018%2822%2900046-7&partnerID=40&md5=c5bf01e65ddafdd4753c7e31f717e5ec |
| Access Level: | Open access |
| Keyword: | abacavir plus lamivudine alanine aminotransferase antiretrovirus agent aspartate aminotransferase bictegravir plus emtricitabine plus tenofovir alafenamide creatinine darunavir dolutegravir efavirenz elvitegravir emtricitabine hemoglobin hepatitis B surface antigen rilpivirine RNA directed DNA polymerase inhibitor tenofovir anti human immunodeficiency virus agent integrase inhibitor raltegravir adult all cause mortality antiretroviral therapy Article CD4 lymphocyte count CD8 lymphocyte count cohort analysis demographics Europe female follow up human Human immunodeficiency virus Human immunodeficiency virus infection major clinical study male mortality mortality rate North America seroconversion virus load Adult Anti-HIV Agents Cohort Studies Darunavir Female HIV Infections HIV Integrase Inhibitors Humans Male Raltegravir Potassium Rilpivirine |
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Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study |
| title |
Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study |
| spellingShingle |
Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study Trickey A. abacavir plus lamivudine alanine aminotransferase antiretrovirus agent aspartate aminotransferase bictegravir plus emtricitabine plus tenofovir alafenamide creatinine darunavir dolutegravir efavirenz elvitegravir emtricitabine hemoglobin hepatitis B surface antigen rilpivirine RNA directed DNA polymerase inhibitor tenofovir anti human immunodeficiency virus agent integrase inhibitor raltegravir adult all cause mortality antiretroviral therapy Article CD4 lymphocyte count CD8 lymphocyte count cohort analysis demographics Europe female follow up human Human immunodeficiency virus Human immunodeficiency virus infection major clinical study male mortality mortality rate North America seroconversion virus load Adult Anti-HIV Agents Cohort Studies Darunavir Female HIV Infections HIV Integrase Inhibitors Humans Male Raltegravir Potassium Rilpivirine |
| title_short |
Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study |
| title_full |
Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study |
| title_fullStr |
Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study |
| title_full_unstemmed |
Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study |
| title_sort |
Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study |
| dc.creator.none.fl_str_mv |
Trickey A. Zhang L. Gill M.J. Bonnet F. Burkholder G. Castagna A. Cavassini M. Cichon P. Crane H. Domingo P. Grabar S. Guest J. Obel N. Psichogiou M. Rava M. Reiss P. Rentsch C.T. Riera M. Schuettfort G. Silverberg M.J. Smith C. Stecher M. Sterling T.R. Ingle S.M. Sabin C.A. Sterne J.A.C. |
| author |
Trickey A. |
| author_facet |
Trickey A. Zhang L. Gill M.J. Bonnet F. Burkholder G. Castagna A. Cavassini M. Cichon P. Crane H. Domingo P. Grabar S. Guest J. Obel N. Psichogiou M. Rava M. Reiss P. Rentsch C.T. Riera M. Schuettfort G. Silverberg M.J. Smith C. Stecher M. Sterling T.R. Ingle S.M. Sabin C.A. Sterne J.A.C. |
| author_role |
author |
| author2 |
Zhang L. Gill M.J. Bonnet F. Burkholder G. Castagna A. Cavassini M. Cichon P. Crane H. Domingo P. Grabar S. Guest J. Obel N. Psichogiou M. Rava M. Reiss P. Rentsch C.T. Riera M. Schuettfort G. Silverberg M.J. Smith C. Stecher M. Sterling T.R. Ingle S.M. Sabin C.A. Sterne J.A.C. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
abacavir plus lamivudine alanine aminotransferase antiretrovirus agent aspartate aminotransferase bictegravir plus emtricitabine plus tenofovir alafenamide creatinine darunavir dolutegravir efavirenz elvitegravir emtricitabine hemoglobin hepatitis B surface antigen rilpivirine RNA directed DNA polymerase inhibitor tenofovir anti human immunodeficiency virus agent integrase inhibitor raltegravir adult all cause mortality antiretroviral therapy Article CD4 lymphocyte count CD8 lymphocyte count cohort analysis demographics Europe female follow up human Human immunodeficiency virus Human immunodeficiency virus infection major clinical study male mortality mortality rate North America seroconversion virus load Adult Anti-HIV Agents Cohort Studies Darunavir Female HIV Infections HIV Integrase Inhibitors Humans Male Raltegravir Potassium Rilpivirine |
| topic |
abacavir plus lamivudine alanine aminotransferase antiretrovirus agent aspartate aminotransferase bictegravir plus emtricitabine plus tenofovir alafenamide creatinine darunavir dolutegravir efavirenz elvitegravir emtricitabine hemoglobin hepatitis B surface antigen rilpivirine RNA directed DNA polymerase inhibitor tenofovir anti human immunodeficiency virus agent integrase inhibitor raltegravir adult all cause mortality antiretroviral therapy Article CD4 lymphocyte count CD8 lymphocyte count cohort analysis demographics Europe female follow up human Human immunodeficiency virus Human immunodeficiency virus infection major clinical study male mortality mortality rate North America seroconversion virus load Adult Anti-HIV Agents Cohort Studies Darunavir Female HIV Infections HIV Integrase Inhibitors Humans Male Raltegravir Potassium Rilpivirine |
| description |
Background: Over the past decade, antiretroviral therapy (ART) regimens that include integrase strand inhibitors (INSTIs) have become the most commonly used for people with HIV starting ART. Although trials and observational studies have compared virological failure on INSTI-based with other regimens, few data are available on mortality in people with HIV treated with INSTIs in routine care. Therefore, we compared all-cause mortality between different INSTI-based and non-INSTI-based regimens in adults with HIV starting ART from 2013 to 2018. Methods: This cohort study used data on people with HIV in Europe and North America from the Antiretroviral Therapy Cohort Collaboration (ART-CC) and UK Collaborative HIV Cohort (UK CHIC). We studied the most common third antiretroviral drugs (additional to nucleoside reverse transcriptase inhibitor) used from 2013 to 2018: rilpivirine, darunavir, raltegravir, elvitegravir, dolutegravir, efavirenz, and others. Adjusted hazard ratios (aHRs; adjusted for clinical and demographic characteristics, comorbid conditions, and other drugs in the regimen) for mortality were estimated using Cox models stratified by ART start year and cohort, with multiple imputation of missing data. Findings: 62 500 ART-naive people with HIV starting ART (12 422 [19·9%] women; median age 38 [IQR 30–48]) were included in the study. 1243 (2·0%) died during 188 952 person-years of follow-up (median 3·0 years [IQR 1·6–4·4]). There was little evidence that mortality rates differed between regimens with dolutegravir, elvitegravir, rilpivirine, darunavir, or efavirenz as the third drug. However, mortality was higher for raltegravir compared with dolutegravir (aHR 1·49, 95% CI 1·15–1·94), elvitegravir (1·86, 1·43–2·42), rilpivirine (1·99, 1·49–2·66), darunavir (1·62, 1·33–1·98), and efavirenz (2·12, 1·60–2·81) regimens. Results were similar for analyses making different assumptions about missing data and consistent across the time periods 2013–15 and 2016–18. Rates of virological suppression were higher for dolutegravir than other third drugs. Interpretation: This large study of patients starting ART since the introduction of INSTIs found little evidence that mortality rates differed between most first-line ART regimens; however, raltegravir-based regimens were associated with higher mortality. Although unmeasured confounding cannot be excluded as an explanation for our findings, virological benefits of first-line INSTIs-based ART might not translate to differences in mortality. Funding: US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council. © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license |
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2022 |
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2022 |
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Inglés |
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ELSEVIER INC |
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Lancet HIV ISSN: 23523018 reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort studyTrickey A.Zhang L.Gill M.J.Bonnet F.Burkholder G.Castagna A.Cavassini M.Cichon P.Crane H.Domingo P.Grabar S.Guest J.Obel N.Psichogiou M.Rava M.Reiss P.Rentsch C.T.Riera M.Schuettfort G.Silverberg M.J.Smith C.Stecher M.Sterling T.R.Ingle S.M.Sabin C.A.Sterne J.A.C.abacavir plus lamivudinealanine aminotransferaseantiretrovirus agentaspartate aminotransferasebictegravir plus emtricitabine plus tenofovir alafenamidecreatininedarunavirdolutegravirefavirenzelvitegraviremtricitabinehemoglobinhepatitis B surface antigenrilpivirineRNA directed DNA polymerase inhibitortenofoviranti human immunodeficiency virus agentintegrase inhibitorraltegraviradultall cause mortalityantiretroviral therapyArticleCD4 lymphocyte countCD8 lymphocyte countcohort analysisdemographicsEuropefemalefollow uphumanHuman immunodeficiency virusHuman immunodeficiency virus infectionmajor clinical studymalemortalitymortality rateNorth Americaseroconversionvirus loadAdultAnti-HIV AgentsCohort StudiesDarunavirFemaleHIV InfectionsHIV Integrase InhibitorsHumansMaleRaltegravir PotassiumRilpivirineBackground: Over the past decade, antiretroviral therapy (ART) regimens that include integrase strand inhibitors (INSTIs) have become the most commonly used for people with HIV starting ART. Although trials and observational studies have compared virological failure on INSTI-based with other regimens, few data are available on mortality in people with HIV treated with INSTIs in routine care. Therefore, we compared all-cause mortality between different INSTI-based and non-INSTI-based regimens in adults with HIV starting ART from 2013 to 2018. Methods: This cohort study used data on people with HIV in Europe and North America from the Antiretroviral Therapy Cohort Collaboration (ART-CC) and UK Collaborative HIV Cohort (UK CHIC). We studied the most common third antiretroviral drugs (additional to nucleoside reverse transcriptase inhibitor) used from 2013 to 2018: rilpivirine, darunavir, raltegravir, elvitegravir, dolutegravir, efavirenz, and others. Adjusted hazard ratios (aHRs; adjusted for clinical and demographic characteristics, comorbid conditions, and other drugs in the regimen) for mortality were estimated using Cox models stratified by ART start year and cohort, with multiple imputation of missing data. Findings: 62 500 ART-naive people with HIV starting ART (12 422 [19·9%] women; median age 38 [IQR 30–48]) were included in the study. 1243 (2·0%) died during 188 952 person-years of follow-up (median 3·0 years [IQR 1·6–4·4]). There was little evidence that mortality rates differed between regimens with dolutegravir, elvitegravir, rilpivirine, darunavir, or efavirenz as the third drug. However, mortality was higher for raltegravir compared with dolutegravir (aHR 1·49, 95% CI 1·15–1·94), elvitegravir (1·86, 1·43–2·42), rilpivirine (1·99, 1·49–2·66), darunavir (1·62, 1·33–1·98), and efavirenz (2·12, 1·60–2·81) regimens. Results were similar for analyses making different assumptions about missing data and consistent across the time periods 2013–15 and 2016–18. Rates of virological suppression were higher for dolutegravir than other third drugs. Interpretation: This large study of patients starting ART since the introduction of INSTIs found little evidence that mortality rates differed between most first-line ART regimens; however, raltegravir-based regimens were associated with higher mortality. Although unmeasured confounding cannot be excluded as an explanation for our findings, virological benefits of first-line INSTIs-based ART might not translate to differences in mortality. Funding: US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council. © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseELSEVIER INC2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15819https://www.scopus.com/inward/record.uri?eid=2-s2.0-85131364296&doi=10.1016%2fS2352-3018%2822%2900046-7&partnerID=40&md5=c5bf01e65ddafdd4753c7e31f717e5ecLancet HIVISSN: 23523018reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p158192026-06-14T12:41:47Z |
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