title: A randomized trial of treatment interruption before optimized antiretroviral therapy for persons with drug-resistant HIV: 48-week virologic results of ACTG A5086.
abstract: BACKGROUND
  The role of structured treatment interruption (STI) before optimized antiretroviral therapy (ART) in patients with drug-resistant human immunodeficiency virus type 1 (HIV-1) is uncertain.
  
  
  METHODS
  AIDS Clinical Trial Group protocol A5086 was a prospective trial of 41 patients with multiple drug class-resistant HIV who were randomized to undergo a 16-week STI followed by optimized ART (STI) or immediate optimized ART (no STI). The primary end point was the proportion of subjects with HIV-1 RNA loads <400 copies/mL 48 weeks after randomization.
  
  
  RESULTS
  Of 39 evaluable patients, 4 (19%) in the STI arm and 6 (33%) in the no STI arm had HIV-1 RNA loads <400 copies/mL at 48 weeks (P=.44). Median changes from baseline in CD4+ cell counts and HIV-1 RNA loads were similar for both arms. Standard genotypes at the end of STI showed nearly complete reversion to wild-type virus in a minority of patients (n=5; 28%). Virus with 3-drug class resistance reemerged even when ART included only 1 or 2 drug classes. Single-genome sequencing showed that each genome encoded resistance mutations for 3 drug classes.
  
  
  CONCLUSIONS
  A 16-week STI before optimized ART did not improve virologic response. Genetic analyses strongly suggest that virologic failure resulted from the reemergence of virus present before STI that encoded 3-drug class resistance on the same genome.
authors.affiliation: University of California, San Diego School of Medicine, San Diego, CA 92103, USA. cbenson@ucsd.edu
authors.forename: Constance A
authors.initials: CA
authors.lastname: Benson
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Downey
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Roy M
authors.initials: RM
authors.lastname: Gulick
authors.forename: Marshall J
authors.initials: MJ
authors.lastname: Glesby
authors.forename: Michael
authors.initials: M
authors.lastname: Wantman
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Bixby
authors.forename: Alex R
authors.initials: AR
authors.lastname: Rinehart
authors.forename: Sally
authors.initials: S
authors.lastname: Snyder
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Sheran
authors.initials: S
authors.lastname: Patel
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents