Lauren Greenberg1, Lene Ryom2, Bastian Neesgaard2, Gilles Wandeler3, Therese Staub4, Martin Gisinger5, Michael Skoll6, Huldrych F Günthard7,8, Alexandra Scherrer7,8, Cristina Mussini9, Colette Smith10, Margaret Johnson10, Stéphane De Wit11, Coca Necsoi11, Christian Pradier12, Ferdinand Wit13, Clara Lehmann14, Antonella d'Arminio Monforte15, Jose M Miró16, Antonella Castagna17, Vincenzo Spagnuolo17, Anders Sönnerborg18, Matthew Law19, Jolie Hutchinson19, Nikoloz Chkhartishvili20, Natalia Bolokadze20, Jan-Christian Wasmuth21, Christoph Stephan22, Vani Vannappagari23, Felipe Rogatto24, Josep M Llibre25, Claudine Duvivier26, Jennifer Hoy27, Mark Bloch19, Heiner C Bucher7, Alexandra Calmy28, Alain Volny Anne29, Annegret Pelchen-Matthews1, Jens D Lundgren2, Lars Peters2, Loveleen Bansi-Matharu1, Amanda Mocroft1. 1. Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, United Kingdom. 2. Centre of Excellence for Health, Immunity and Infections (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 3. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland. 4. Infectious Diseases, Centre Hospitalier Luxembourg (CHL), Luxembourg City, Luxembourg. 5. Medizinische Universität Innsbruck , Innsbruck, Austria. 6. Wiener Medizinische Universität, Vienna, Austria. 7. Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland. 8. Institute of Medical Virology, University of Zurich, Zurich, Switzerland. 9. Modena HIV Cohort, Università degli Studi di Modena , Modena, Italy. 10. Royal Free HIV Cohort Study, Royal Free Hospital, University College London, London, United Kingdom. 11. Saint Pierre University Hospital, Université Libre de Bruxelles , Brussels, Belgium. 12. Nice HIV Cohort, Université Côte d'Azur et Centre Hospitalier Universitaire, Nice, France. 13. AIDS Therapy Evaluation in the Netherlands Cohort (ATHENA), Stichting HIV Monitoring (SHM), Amsterdam, The Netherlands. 14. University Hospital Cologne, Cologne, Germany. 15. Italian Cohort Naive Antiretrovirals, (ICONA) L'Azienda Socio Sanitaria Territoriale (ASST) Santi Paolo e Carlo , Milano, Italy. 16. Hospital Clinic-August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain. 17. School of Medicine, Vita-Salute San Raffaele University, Milan, Italy. 18. Division of Infectious Diseases, Karolinska Institutet and Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden. 19. Australian HIV Observational Database (AHOD), University of New South Wales (UNSW) , Sydney Australia. 20. Georgian National AIDS Health Information System (AIDS HIS), Infectious Diseases, AIDS and Clinical Immunology Research Center , Tbilisi, Georgia. 21. University Hospital Bonn, Bonn, Germany. 22. Medical Department No. 2, Infectious Diseases Unit, Goethe-University Hospital Frankfurt, Frankfurt, Germany. 23. ViiV Healthcare, RTP, Research Triangle Park, North Carolina, USA. 24. Gilead science, Foster City, California, USA. 25. Hospital Universitari Germans Trias i Pujol Department of Internal Medicine, HIV Unit, Barcelona, Spain. 26. Assistance Publique - Hôpitaux de Paris (APHP)-Hôpital Necker-Enfants Malades, Service de Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker-Pasteur, Institut hospitalo-universitaire (IHU) Imagine , Paris, France. 27. Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Victoria, Australia. 28. HIV/AIDS Unit in Geneva University Hospital, Geneva, Switzerland. 29. European AIDS Treatment Group, Brussels, Belgium.
Abstract
BACKGROUND: Limited data exist that compare clinical outcomes of 2-drug regimens (2DRs) and 3-drug regimens (3DRs) in people living with human immunodeficiency virus. METHODS: Antiretroviral treatment-experienced individuals in the International Cohort Consortium of Infectious Diseases (RESPOND) who switched to a new 2DR or 3DR from 1 January 2012-1 October 2018 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression. RESULTS: Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) started 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median, 52.6 years [interquartile range, 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%). There were 619 events during 27 159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU; 95% confidence interval [CI]: 20.7-24.5) on 3DRs and 79 (30.9/1000 PYFU; 95% CI: 24.8-38.5) on 2DRs. The most common events were death (7.5/1000 PYFU; 95% CI: 6.5-8.6) and non-AIDS cancer (5.8/1000 PYFU; 95% CI: 4.9-6.8). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio, 0.92; 95% CI: .72-1.19; P = .53). CONCLUSIONS: This is the first large, international cohort to assess clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes. Further research on resistance barriers and long-term durability of 2DRs is needed.
BACKGROUND: Limited data exist that compare clinical outcomes of 2-drug regimens (2DRs) and 3-drug regimens (3DRs) in people living with human immunodeficiency virus. METHODS: Antiretroviral treatment-experienced individuals in the International Cohort Consortium of Infectious Diseases (RESPOND) who switched to a new 2DR or 3DR from 1 January 2012-1 October 2018 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression. RESULTS: Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) started 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median, 52.6 years [interquartile range, 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%). There were 619 events during 27 159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU; 95% confidence interval [CI]: 20.7-24.5) on 3DRs and 79 (30.9/1000 PYFU; 95% CI: 24.8-38.5) on 2DRs. The most common events were death (7.5/1000 PYFU; 95% CI: 6.5-8.6) and non-AIDS cancer (5.8/1000 PYFU; 95% CI: 4.9-6.8). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio, 0.92; 95% CI: .72-1.19; P = .53). CONCLUSIONS: This is the first large, international cohort to assess clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes. Further research on resistance barriers and long-term durability of 2DRs is needed.
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