title: High virological failure rate in HIV patients after switching to a regimen with two nucleoside reverse transcriptase inhibitors plus tenofovir.
abstract: BACKGROUND
  Regimens with two nucleoside analogue reverse transcriptase inhibitors (NRTI) plus tenofovir DF have been associated with a high failure rate when administered as first line therapy. Little is known about patients with undetectable viral loads who are switched to these regimens.
  
  
  METHODS
  A post-hoc review of the virological outcomes at 24 weeks of patients who switched from a successful (< 50 copies/ml) highly active antiretroviral therapy regimen to a tenofovir plus two NRTI combination.
  
  
  RESULTS
  Fifty-five patients started a two NRTI plus tenofovir regimen mostly because of previous toxicity/intolerance of the original drugs (74%). After 24 weeks, only 17 patients (31%) remained virologically suppressed. Patients with a regimen including a didanosine plus tenofovir-based regimen had significantly poorer outcomes than those on other combinations (success rate 5 versus 47.1%, P = 0.001). In contrast, patients on a regimen including zidovudine plus tenofovir showed a trend towards a better outcome (75 versus 27%, P = 0.083). Multivariate analysis confirmed the combination of didanosine plus tenofovir as the only variable associated with a higher rate of failure (odds ratio 17.7; 95% confidence interval 2.1-147; P = 0.007). Patients with previous reverse transcriptase mutations presented virological failure in all cases. At failure a new pattern, including the K65R mutation with M184V or thymidine analogue mutations, was observed.
  
  
  CONCLUSIONS
  Even in patients with suppressed viraemia, a two NRTI plus tenofovir regimen is associated with a high virological failure rate, but significant variations are found depending on the nucleosides included.
authors.affiliation: Infectious Diseases Unit, Hospital Ramón y Cajal, Madrid, Spain. mjperez@telefonica.net
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Pérez-Elías
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
authors.forename: Carolina
authors.initials: C
authors.lastname: Gutiérrez
authors.forename: Dolores
authors.initials: D
authors.lastname: López
authors.forename: Victor
authors.initials: V
authors.lastname: Abraira
authors.forename: Ana
authors.initials: A
authors.lastname: Moreno
authors.forename: Fernando
authors.initials: F
authors.lastname: Dronda
authors.forename: Jóse Luis
authors.initials: JL
authors.lastname: Casado
authors.forename: Antonio
authors.initials: A
authors.lastname: Antela
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Rodríguez
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D016049:Didanosine / Q000627:therapeutic use*; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D005500:Follow-Up Studies; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D063065:Organophosphonates / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D000068698:Tenofovir; D000225:Adenine; D016049:Didanosine