title: Phenotypic susceptibility to didanosine is associated with antiviral activity in treatment-experienced patients with HIV-1 infection.
abstract: OBJECTIVE
  We investigated the relationship between human immunodeficiency virus (HIV) phenotypic susceptibility to didanosine and the antiviral activity of didanosine (ddI) in the JAGUAR study.
  
  
  METHODS
  Baseline plasma HIV phenotypic susceptibility to ddI was assessed using a phenotype assay of patients randomized to receive ddI or placebo for 4 weeks in addition to their current regimen. Phenotypic susceptibility scores (PSSs) were then calculated for each sample. Associations between PSS and week 4 reductions in plasma HIV-1 RNA load or virologic response were assessed using linear regression and Jonckherre's test and the Wilcoxon and Cochran-Armitage tests, respectively.
  
  
  RESULTS
  In the ddI arm, a significant association between reduction in viral load and continuous PSS was observed (P<.0001). Using distinct categories, an increasing fold change (FC) in susceptibility to ddI was strongly associated with smaller reductions in plasma HIV-1 RNA load (P<.0001). The proportion of virologic responders was 83% (15/18) for patients with a ddI FC < or =1.3, 50% (33/66) for patients with an FC of 1.3-2.2, and 29% (4/14) for patients with an FC > or =2.2 (P=.0008). After we determined these findings, 3 ddI FC categories were defined using 1.3 and 2.2 as thresholds.
  
  
  CONCLUSIONS
  The relationship between phenotypic susceptibility to ddI and reduction in plasma HIV-1 RNA load describes a continuum. The establishment of a lower clinical cutoff at 1.3 and an upper clinical cutoff at 2.2 are clinically relevant.
authors.affiliation: Unité INSERM U720, BP 335-75625, Paris, France. pflandre@ccde.chups.jussieu.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Flandre
authors.forename: Colombe
authors.initials: C
authors.lastname: Chappey
authors.forename: Anne Genevieve
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Kirk
authors.initials: K
authors.lastname: Ryan
authors.forename: Jen-Fue
authors.initials: JF
authors.lastname: Maa
authors.forename: Mike
authors.initials: M
authors.lastname: Bates
authors.forename: Daniel
authors.initials: D
authors.lastname: Seekins
authors.forename: Marie Charlotte
authors.initials: MC
authors.lastname: Bernard
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Molina
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016049:Didanosine / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D013045:Species Specificity; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D016049:Didanosine