Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study
Por:
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.
Publicada:
1 ene 2022
Resumen:
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
Filiaciones:
Trickey A.:
Population Health Sciences, University of Bristol, Bristol, United Kingdom
Zhang L.:
Population Health Sciences, University of Bristol, Bristol, United Kingdom
Gill M.J.:
Department of Medicine, University of Calgary, South Alberta HIV Clinic, Calgary, AB, Canada
Bonnet F.:
University of Bordeaux, Institut de santé publique, d’épidémiologie et de développement, Institut National de la Santé et de la Recherche Médicale (INSERM) U1219, Bordeaux, France
Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
Burkholder G.:
Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, United States
Castagna A.:
Institute of Infectious Diseases, University vita E Salute, Milan, Italy
Cavassini M.:
Division of Infectious Diseases, Lausanne University Hospital, Lausanne, Switzerland
Cichon P.:
Infectious Diseases Outpatient Clinic, Otto-Wagner Hospital, Vienna, Austria
Crane H.:
Division of Infectious Diseases, Department of Medicine University of Washington, Seattle, WA, United States
Domingo P.:
Department of Infectious Diseases, Santa Creu i Sant Pau Hospital, Barcelona, Spain
Grabar S.:
Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France
Department of Public Health, AP-HP, St Antoine Hospital, Paris, France
Guest J.:
Atlanta Veterans Association Medical Center, Decatur, GA, United States
Rollins School of Public Health at Emory University, Atlanta, GA, United States
Obel N.:
Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Rigshospitalet, Denmark
Psichogiou M.:
First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
Rava M.:
Unit AIDS Research Network Cohort, National Center of Epidemiology, Health Institute Carlos III, Madrid, Spain
Reiss P.:
Stichting HIV Monitoring, Amsterdam, Netherlands
Department of Global Health, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands
Rentsch C.T.:
Yale School of Medicine, Yale University, New Haven, CT, United States
VA Connecticut Healthcare System, West Haven, CT, United States
Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom
Riera M.:
Fundación Instituto de Investigación Sanitaria Illes Balears, Infectious Diseases Unit, Mallorca, Hospital Son Espases, Spain
Schuettfort G.:
Infectious Diseases Unit, Medical Center 2, Frankfurt University Hospital, Frankfurt, Germany
Silverberg M.J.:
Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States
Smith C.:
Department of Infection and Population Health, University College London, London, United Kingdom
Stecher M.:
Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
German Center for Infection Research, Partner Site Cologne–Bonn, Cologne, Germany
Sterling T.R.:
Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States
Ingle S.M.:
Population Health Sciences, University of Bristol, Bristol, United Kingdom
Sabin C.A.:
Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, London, United Kingdom
Sterne J.A.C.:
Population Health Sciences, University of Bristol, Bristol, United Kingdom
All Open Access, Hybrid Gold
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