title: Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial.
abstract: BACKGROUND
  Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting.
  
  
  RESULTS
  We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log(10) copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86-1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68-1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options.
  
  
  CONCLUSIONS
  We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00050089.
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, California, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Holodniy
authors.forename: Sheldon T
authors.initials: ST
authors.lastname: Brown
authors.forename: D William
authors.initials: DW
authors.lastname: Cameron
authors.forename: Tassos C
authors.initials: TC
authors.lastname: Kyriakides
authors.forename: Brian
authors.initials: B
authors.lastname: Angus
authors.forename: Abdel
authors.initials: A
authors.lastname: Babiker
authors.forename: Joel
authors.initials: J
authors.lastname: Singer
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Owens
authors.forename: Aslam
authors.initials: A
authors.lastname: Anis
authors.forename: Ruth
authors.initials: R
authors.lastname: Goodall
authors.forename: Fleur
authors.initials: F
authors.lastname: Hudson
authors.forename: Mirek
authors.initials: M
authors.lastname: Piaseczny
authors.forename: John
authors.initials: J
authors.lastname: Russo
authors.forename: Martin
authors.initials: M
authors.lastname: Schechter
authors.forename: Lawrence
authors.initials: L
authors.lastname: Deyton
authors.forename: Janet
authors.initials: J
authors.lastname: Darbyshire
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D019380:Anti-HIV Agents