title: Increased virological failure in naive HIV-1-infected patients taking lamivudine compared with emtricitabine in combination with tenofovir and efavirenz or nevirapine in the Dutch nationwide ATHENA cohort.
abstract: BACKGROUND
  Guidelines for treatment of human immunodeficiency virus type 1 (HIV-1) infection consider lamivudine and emtricitabine to be interchangeable components in first-line combination antiretroviral therapy (cART). The evidence for their clinical equivalence in cART is inconsistent. The primary aim of this study was to evaluate the virological responses to lamivudine and emtricitabine in recommended cART.
  
  
  METHODS
  This was an observational study using data from the AIDS Therapy Evaluation in the Netherlands (ATHENA) nationwide HIV cohort. The virological responses to lamivudine and emtricitabine were compared by multivariable adjusted logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score-adjusted models.
  
  
  RESULTS
  Therapy-naive HIV-1-infected patients without baseline resistance (N = 4740) initiated lamivudine or emtricitabine with efavirenz/tenofovir or nevirapine/tenofovir. The use of lamivudine was associated with more virological failure at week 48 compared to emtricitabine with efavirenz/tenofovir (10.8% vs 3.6%; adjusted odds ratio [AOR], 1.78; 95% confidence interval [CI], 1.11-2.84) and nevirapine/tenofovir (27% vs 11%; AOR, 2.09; 95% CI, 1.25-3.52) in on-treatment analysis. Propensity score-adjusted models and intent-to-treat sensitivity analyses gave comparable results. The adjusted hazard ratio of virological failure at week 240 using lamivudine instead of emtricitabine was 2.35 (95% CI, 1.61-3.42) with efavirenz and 2.01 (95% CI, 1.36-2.98) with nevirapine. The inclusion of lamivudine or emtricitabine in cART did not influence the time to virological suppression within 48 weeks or the probability of virological rebound after successful virological suppression.
  
  
  CONCLUSIONS
  The use of emtricitabine instead of lamivudine as part of cART was associated with better virological responses. These findings are relevant for settings with extensive use of lamivudine and for settings where generic lamivudine will be available.
authors.affiliation: Departments of Internal Medicine and Infectious Diseases.
authors.forename: Casper
authors.initials: C
authors.lastname: Rokx
authors.affiliation: Virology, Erasmus University Medical Center, Rotterdam.
authors.forename: Azzania
authors.initials: A
authors.lastname: Fibriani
authors.affiliation: Virology, Erasmus University Medical Center, Rotterdam.
authors.forename: David A M C
authors.initials: DA
authors.lastname: van de Vijver
authors.affiliation: Departments of Internal Medicine and Infectious Diseases.
authors.forename: Annelies
authors.initials: A
authors.lastname: Verbon
authors.affiliation: Virology, Erasmus University Medical Center, Rotterdam.
authors.forename: Martin
authors.initials: M
authors.lastname: Schutten
authors.affiliation: Stichting HIV Monitoring, Amsterdam, The Netherlands.
authors.forename: Luuk
authors.initials: L
authors.lastname: Gras
authors.affiliation: Departments of Internal Medicine and Infectious Diseases.
authors.forename: Bart J A
authors.initials: BJ
authors.lastname: Rijnders
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents
keywords: HIV-1; antiretroviral therapy; emtricitabine; lamivudine; virological failure