title: Failures of 1 week on, 1 week off antiretroviral therapies in a randomized trial.
abstract: BACKGROUND
  Scheduled treatment interruptions are being evaluated in an effort to decrease costs and side effects of highly active antiretroviral therapy (HAART). A schedule of 1 week on and 1 week off therapy offers the promise of 50% less drug exposure with continuously undetectable HIV RNA concentration.
  
  
  METHODS
  In the Staccato study 600 patients on successful HAART were to be randomized to either continued therapy, CD4-guided therapy, or one week on, one week off therapy. A scheduled preliminary analysis evaluated effectiveness in the 1-week-on-1-week-off arm.
  
  
  RESULTS
  Of 36 evaluable patients, 19 (53%) had two successive HIV RNA concentrations > 500 copies/ml at the end of the week off therapy, and were classified as virological failure. Most of those who failed took didanosine, stavudine, saquinavir, and ritonavir (11 patients). In these patients, there was no evidence of mutations suggestive of drug resistance, and plasma saquinavir levels were within the expected range. Two of three patients failing on triple nucleotides had drug resistance mutations, but nonetheless responded to reintroduction of triple nucleotide therapy. One of two patients taking nevirapine, and one of eight taking efavirenz, also failed. Both had resistance mutations at the time of failure, but not at baseline.
  
  
  CONCLUSIONS
  The 1-week-on-1-week-off schedule, as tested in the Staccato study, showed an unacceptably high failure rate and was therefore terminated.
authors.affiliation: HIVNAT (The HIV Netherlands Australia Thailand Research Collaboration), Thai Red Cross AIDS Research Center.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Reto
authors.initials: R
authors.lastname: Nuesch
authors.forename: Michelle
authors.initials: M
authors.lastname: Le Braz
authors.forename: Ploechan
authors.initials: P
authors.lastname: Chetchotisakd
authors.forename: Asda
authors.initials: A
authors.lastname: Vibhagool
authors.forename: Saijai
authors.initials: S
authors.lastname: Wicharuk
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: David
authors.initials: D
authors.lastname: Cooper
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: E
authors.initials: E
authors.lastname: Bernasconi
authors.forename: M
authors.initials: M
authors.lastname: Cavassini
authors.forename: C
authors.initials: C
authors.lastname: Ebnöther
authors.forename: C
authors.initials: C
authors.lastname: Fagard
authors.forename: D
authors.initials: D
authors.lastname: Genné
authors.forename: N
authors.initials: N
authors.lastname: Khanna
authors.forename: L
authors.initials: L
authors.lastname: Perrin
authors.forename: P
authors.initials: P
authors.lastname: Phanupak
authors.forename: S
authors.initials: S
authors.lastname: Ubolyam
authors.forename: P
authors.initials: P
authors.lastname: Vernazza
authors.forename: S
authors.initials: S
authors.lastname: Yerly
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D016049:Didanosine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005814:Genes, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000008:administration & dosage; D019258:Saquinavir / Q000008:administration & dosage; D018119:Stavudine / Q000008:administration & dosage; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018119:Stavudine; D016049:Didanosine; D019258:Saquinavir; D019438:Ritonavir