title: Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study.
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.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Wan-Lin
authors.initials: WL
authors.lastname: Yang
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kouyos
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Alexandra U
authors.initials: AU
authors.lastname: Scherrer
authors.affiliation: Swiss National Center for Retroviruses, Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Böni
authors.affiliation: Swiss National Center for Retroviruses, Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Cyril
authors.initials: C
authors.lastname: Shah
authors.affiliation: Laboratory of Virology, Division of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.affiliation: Department of Biomedicine-Petersplatz, University of Basel, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klimkait
authors.affiliation: Division of Immunology and Allergy, University Hospital Lausanne, Lausanne, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Aubert
authors.affiliation: Department of Infectious Diseases, Berne University Hospital and University of Berne, Berne, Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Hirzel
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.affiliation: Division of Infectious Diseases, University Hospital Lausanne, Lausanne, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.affiliation: Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.affiliation: Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen, Switzerland.
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.affiliation: Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Held
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.affiliation: 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.
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000627:therapeutic use*; D009711:Nucleotides / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013557:Switzerland; D017211:Treatment Failure
chemical_list: D009705:Nucleosides; D009711:Nucleotides; D018894:Reverse Transcriptase Inhibitors