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...

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Authors: 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.
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
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85131364296&doi=10.1016%2fS2352-3018%2822%2900046-7&partnerID=40&md5=c5bf01e65ddafdd4753c7e31f717e5ec
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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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dc.title.none.fl_str_mv 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
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv 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
url 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
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER INC
publisher.none.fl_str_mv ELSEVIER INC
dc.source.none.fl_str_mv Lancet HIV
ISSN: 23523018
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
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spelling 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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