Wan-Lin Yang1, Roger D Kouyos1, Alexandra U Scherrer1, Jürg Böni2, Cyril Shah2, Sabine Yerly3, Thomas Klimkait4, Vincent Aubert5, Cédric Hirzel6, Manuel Battegay7, Matthias Cavassini8, Enos Bernasconi9, Pietro Vernazza10, Leonhard Held11, Bruno Ledergerber1, Huldrych F Günthard12. 1. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland Institute of Medical Virology, University of Zurich, Zurich, Switzerland. 2. Swiss National Center for Retroviruses, Institute of Medical Virology, University of Zurich, Zurich, Switzerland. 3. Laboratory of Virology, Division of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland. 4. Department of Biomedicine-Petersplatz, University of Basel, Basel, Switzerland. 5. Division of Immunology and Allergy, University Hospital Lausanne, Lausanne, Switzerland. 6. Department of Infectious Diseases, Berne University Hospital and University of Berne, Berne, Switzerland. 7. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland. 8. Division of Infectious Diseases, University Hospital Lausanne, Lausanne, Switzerland. 9. Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland. 10. Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland. 11. Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland. 12. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland Institute of Medical Virology, University of Zurich, Zurich, Switzerland huldrych.guenthard@usz.ch.
Abstract
BACKGROUND: The most recommended NRTI combinations as first-line antiretroviral treatment for HIV-1 infection in resource-rich settings are tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. Efficacy studies of these combinations also considering pill numbers, dosing frequencies and ethnicities are rare. METHODS: We included patients starting first-line combination ART (cART) with or switching from first-line cART without treatment failure to tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine plus efavirenz or nevirapine. Cox proportional hazards regression was used to investigate the effect of the different NRTI combinations on two primary outcomes: virological failure (VF) and emergence of NRTI resistance. Additionally, we performed a pill burden analysis and adjusted the model for pill number and dosing frequency. RESULTS: Failure events per treated patient for the four NRTI combinations were as follows: 19/1858 (tenofovir/emtricitabine), 9/387 (abacavir/lamivudine), 11/344 (tenofovir/lamivudine) and 45/1244 (zidovudine/lamivudine). Compared with tenofovir/emtricitabine, abacavir/lamivudine had an adjusted HR for having VF of 2.01 (95% CI 0.86-4.55), tenofovir/lamivudine 2.89 (1.22-6.88) and zidovudine/lamivudine 2.28 (1.01-5.14), whereas for the emergence of NRTI resistance abacavir/lamivudine had an HR of 1.17 (0.11-12.2), tenofovir/lamivudine 11.3 (2.34-55.3) and zidovudine/lamivudine 4.02 (0.78-20.7). Differences among regimens disappeared when models were additionally adjusted for pill burden. However, non-white patients compared with white patients and higher pill number per day were associated with increased risks of VF and emergence of NRTI resistance: HR of non-white ethnicity for VF was 2.85 (1.64-4.96) and for NRTI resistance 3.54 (1.20-10.4); HR of pill burden for VF was 1.41 (1.01-1.96) and for NRTI resistance 1.72 (0.97-3.02). CONCLUSIONS: Although VF and emergence of resistance was very low in the population studied, tenofovir/emtricitabine appears to be superior to abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. However, it is unclear whether these differences are due to the substances as such or to an association of tenofovir/emtricitabine regimens with lower pill burden.
BACKGROUND: The most recommended NRTI combinations as first-line antiretroviral treatment for HIV-1 infection in resource-rich settings are tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. Efficacy studies of these combinations also considering pill numbers, dosing frequencies and ethnicities are rare. METHODS: We included patients starting first-line combination ART (cART) with or switching from first-line cART without treatment failure to tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine plus efavirenz or nevirapine. Cox proportional hazards regression was used to investigate the effect of the different NRTI combinations on two primary outcomes: virological failure (VF) and emergence of NRTI resistance. Additionally, we performed a pill burden analysis and adjusted the model for pill number and dosing frequency. RESULTS: Failure events per treated patient for the four NRTI combinations were as follows: 19/1858 (tenofovir/emtricitabine), 9/387 (abacavir/lamivudine), 11/344 (tenofovir/lamivudine) and 45/1244 (zidovudine/lamivudine). Compared with tenofovir/emtricitabine, abacavir/lamivudine had an adjusted HR for having VF of 2.01 (95% CI 0.86-4.55), tenofovir/lamivudine 2.89 (1.22-6.88) and zidovudine/lamivudine 2.28 (1.01-5.14), whereas for the emergence of NRTI resistance abacavir/lamivudine had an HR of 1.17 (0.11-12.2), tenofovir/lamivudine 11.3 (2.34-55.3) and zidovudine/lamivudine 4.02 (0.78-20.7). Differences among regimens disappeared when models were additionally adjusted for pill burden. However, non-white patients compared with white patients and higher pill number per day were associated with increased risks of VF and emergence of NRTI resistance: HR of non-white ethnicity for VF was 2.85 (1.64-4.96) and for NRTI resistance 3.54 (1.20-10.4); HR of pill burden for VF was 1.41 (1.01-1.96) and for NRTI resistance 1.72 (0.97-3.02). CONCLUSIONS: Although VF and emergence of resistance was very low in the population studied, tenofovir/emtricitabine appears to be superior to abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. However, it is unclear whether these differences are due to the substances as such or to an association of tenofovir/emtricitabine regimens with lower pill burden.
Authors: J Gregson; S Y Rhee; R Datir; D Pillay; C F Perno; A Derache; R S Shafer; R K Gupta Journal: J Infect Dis Date: 2020-09-01 Impact factor: 5.226
Authors: Susana Posada-Céspedes; Gert Van Zyl; Hesam Montazeri; Jack Kuipers; Soo-Yon Rhee; Roger Kouyos; Huldrych F Günthard; Niko Beerenwinkel Journal: PLoS Comput Biol Date: 2021-09-07 Impact factor: 4.475
Authors: Nikolas Friedrich; Emanuel Stiegeler; Matthias Glögl; Thomas Lemmin; Simon Hansen; Claus Kadelka; Yufan Wu; Patrick Ernst; Liridona Maliqi; Caio Foulkes; Mylène Morin; Mustafa Eroglu; Thomas Liechti; Branislav Ivan; Thomas Reinberg; Jonas V Schaefer; Umut Karakus; Stephan Ursprung; Axel Mann; Peter Rusert; Roger D Kouyos; John A Robinson; Huldrych F Günthard; Andreas Plückthun; Alexandra Trkola Journal: Nat Commun Date: 2021-11-18 Impact factor: 14.919