title: No benefit of a structured treatment interruption based on genotypic resistance in heavily pretreated HIV-infected patients.
abstract: OBJECTIVE
  To evaluate the potential benefits of a tailored antiretroviral treatment interruption with duration based on the observed reversion of resistance mutations.
  
  
  METHODS
  In this open single-arm pilot study, 23 patients with multiple treatment failure interrupted therapy and underwent longitudinal genotypic resistance testing. Salvage gigatherapy was started when resistance mutations to at least two antiretroviral drug classes reverted. The primary endpoint was a fall in viral load by > 1 log10 copies/ml after 12 weeks of salvage therapy.
  
  
  RESULTS
  Baseline median viral load was 5.14 log copies/ml and CD4 cell count 43 x 10 cells/l. Genotypic resistance testing showed a median of six, two and nine resistance mutations to nucleoside analogue reverse transcriptase inhibitors, non-nucleoside analogue reverse transcriptase inhibitors and protease inhibitors, respectively; viral strains were susceptible to no more than one drug in 17/23 patients. The median duration of treatment interruption was 24 weeks (range, 12-37), leading to median changes from baseline of + 0.54 log10 copies/ml and -30 x 10(6) cells/l. At the end of treatment interruption, plasma HIV was susceptible to at least three drugs in 16/23 patients. After 12 weeks of salvage multitherapy, only one patient had a decrease in viral load > 1 log copies/ml. All baseline resistance mutations recurred after treatment resumption. AIDS-defining events occurred in two-thirds of patients during the study period.
  
  
  CONCLUSIONS
  In HIV-infected patients with multiple failures and no therapeutic options at baseline, significant reversion of resistance mutations after prolonged treatment interruption failed to restore antiviral efficacy of a salvage regimen and was clinically deleterious.
authors.affiliation: Department of Infectious and Tropical Diseases, Hospital Pitié-Salpétrière, Paris, France.
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.forename: Marc
authors.initials: M
authors.lastname: Wirden
authors.forename: Nadine
authors.initials: N
authors.lastname: Ktorza
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Hocine
authors.initials: H
authors.lastname: Aït-Mohand
authors.forename: Luminita
authors.initials: L
authors.lastname: Schneider
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dominguez
authors.forename: François
authors.initials: F
authors.lastname: Bricaire
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D009154:Mutation; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D016879:Salvage Therapy / Q000379:methods; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral