title: Didanosine in HIV-1-infected patients experiencing failure of antiretroviral therapy: a randomized placebo-controlled trial.
abstract: BACKGROUND
  The antiviral efficacy of didanosine in patients experiencing virological failure is not well known.
  
  
  METHODS
  A total of 168 patients (139 men and 29 women) receiving stable antiretroviral therapy with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 1000-100,000 copies/mL were randomly assigned to have didanosine (n=111) or placebo (n=57) added to their currently failing regimen for 4 weeks. The primary efficacy end point was the change in HIV-1 RNA level from baseline to week 4.
  
  
  RESULTS
  At baseline, the median HIV-1 RNA level was 3.8 log(10) copies/mL, the median CD4 cell count was 378 cells/mm(3), and the median number of nucleoside reverse-transcriptase inhibitor-associated mutations (NAMs) was 4. At week 4, a significant decrease in the median HIV-1 RNA level was observed in the didanosine group, compared with that in the placebo group (-0.56 vs. +0.07 log(10) copies/mL, respectively) (P<.0001). A total of 33 patients (31%) in the didanosine group, compared with 3 (6%) in the placebo group, had HIV-1 RNA levels <400 copies/mL (P<.001). Significant antiviral activity of didanosine was observed in patients with up to 5 NAMs at baseline. Diarrhea occurred in 5 patients (5%) in the didanosine group and 2 patients (4%) in the placebo group.
  
  
  CONCLUSIONS
  In HIV-1-infected patients experiencing failure of antiretroviral therapy, didanosine retains short-term antiviral activity.
authors.affiliation: Department of Infectious Diseases, Saint-Louis Hospital, Paris, France. jean-michel.molina@sls.ap-hop-paris.fr
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Juliette
authors.initials: J
authors.lastname: Pavie
authors.forename: Laurence
authors.initials: L
authors.lastname: Heripret
authors.forename: Corinne Merle
authors.initials: CM
authors.lastname: De Boever
authors.forename: Martine
authors.initials: M
authors.lastname: Troccaz
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Leleu
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016049:Didanosine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016049:Didanosine