title: Two-months-off, four-months-on antiretroviral regimen increases the risk of resistance, compared with continuous therapy: a randomized trial involving West African adults.
abstract: BACKGROUND
  A randomized trial was launched in Côte d'Ivoire in 2002 to compare continuous antiretroviral treatment (hereafter, "C-ART") to an ART regimen of 2 months off and 4 months on therapy (hereafter, "2/4-ART"). We report the final analysis.
  
  
  METHODS
  A total of 435 adults who were receiving successful ART ((median CD4 cell count prior to ART, 272 cells/mm(3); 88% were receiving a zidovudine-lamivudine-efavirenz regimen) were randomized to receive C-ART or 2/4-ART. The main primary end point was the percentage of patients with <350 CD4 cells/mm(3) at 24 months. The sample size ensured 80% power to demonstrate noninferiority (noninferiority bound, -15%), assuming that 30% of the patients in the C-ART arm would have <350 CD4 cells/mm(3). Other end points were mortality, morbidity, cost of care, genotypic resistance, adherence, and toxicity.
  
  
  RESULTS
  The percentage of patients with <350 CD4 cells/mm(3) at 24 months was 5.6% (6 of 107) in the C-ART arm and 14.6% (46 of 315) in the 2/4-ART arm (lower bound of the 95% CI for the difference, -14%). Cost was 18% higher in the C-ART arm, and resistance to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was 20% higher in the 2/4-ART arm. Other end points were nonconclusive.
  
  
  CONCLUSIONS
  Although 2/4-ART met the predetermined criteria for noninferiority, the percentage of patients with <350 CD4 cells/mm(3) in the C-ART arm was lower than anticipated, which makes the clinical significance of this noninferiority uncertain. In addition, 2/4-ART led to an unacceptable additional risk of selecting for drug-resistant virus. This new argument against episodic ART strategies is also a caveat against any unplanned ART interruptions in Africa, where most patients receive NNRTIs.
authors.affiliation: INSERM, Unité 897, Centre de Recherche Epidémiologie et Biostatistique, Bordeaux, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Danel
authors.forename: Raoul
authors.initials: R
authors.lastname: Moh
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.forename: Delphine
authors.initials: D
authors.lastname: Gabillard
authors.forename: Joachim
authors.initials: J
authors.lastname: Gnokoro
authors.forename: Charles-Joseph
authors.initials: CJ
authors.lastname: Diby
authors.forename: Thomas
authors.initials: T
authors.lastname: Toni
authors.forename: Lambert
authors.initials: L
authors.lastname: Dohoun
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bissagnene
authors.forename: Roger
authors.initials: R
authors.lastname: Salamon
authors.forename: Xavier
authors.initials: X
authors.lastname: Anglaret
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D007560:Cote d'Ivoire / Q000453:epidemiology; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000502:physiology; D005260:Female; D006678:HIV / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007182:Income; D008297:Male; D009154:Mutation; D011897:Random Allocation; D016896:Treatment Outcome; D019562:Viral Load; D014765:Viral Vaccines / Q000627:therapeutic use
chemical_list: D044966:Anti-Retroviral Agents; D014765:Viral Vaccines