title: Didanosine compared with continued zidovudine therapy for HIV-infected patients with 200 to 500 CD4 cells/mm3. A double-blind, randomized, controlled trial. Canadian HIV Trials Network Protocol 002 Study Group.
abstract: OBJECTIVE
  To compare the safety and efficacy of didanosine with that of continued zidovudine therapy in persons with human immunodeficiency virus (HIV) infection who had received zidovudine for at least 6 months and had CD4 cell counts of 200 to 500 CD4 cells/mm3.
  
  
  METHODS
  Double-blind, randomized controlled trial.
  
  
  METHODS
  10 Canadian university-affiliated specialty clinics.
  
  
  METHODS
  246 patients were assigned to receive standard doses of either zidovudine or didanosine.
  
  
  METHODS
  The primary clinical end point was the occurrence of a new, previously undiagnosed acquired immunodeficiency syndrome (AIDS)-defining illness or death.
  
  
  RESULTS
  245 of 246 patients were eligible (118 receiving didanosine and 127 receiving zidovudine). Sixty-six percent were asymptomatic, 30% had AIDS-related complex, and 4% had AIDS. The median baseline CD4 count was 320 cells/mm3. The median previous duration of zidovudine therapy was 471 days. Nine new AIDS-defining illnesses developed during the study; all but one were in the zidovudine group (relative risk, 7.9 [95% CI, 1.0 to 63.3; P = 0.02]). A change to didanosine led to a statistically significant increase in CD4 counts by week 2 that persisted until the end of the study at week 48 (P < or = 0.01). Viral sensitivity studies (done in 102 patients) showed that 28% of the zidovudine group and 21% of the didanosine group had high-level in vitro resistance to zidovudine (50% inhibitory concentration greater than 0.8 microM) at baseline (P = 0.49). Only one patient in the didanosine group developed high-level resistance to zidovudine during the study. In the zidovudine group, the cumulative probability of developing high-level resistance to zidovudine was 59% at 1 year (P = 0.01). Abdominal pain, leukopenia, and neutropenia were more frequent in the zidovudine group, and hyperuricemia was more frequent in the didanosine group (P < 0.05).
  
  
  CONCLUSIONS
  In clinically stable patients with 200 to 500 CD4 cells/mm3 who had tolerated zidovudine for at least 6 months, a change to didanosine led to a decrease in the rate of disease progression, a sustained increase in CD4 counts, and a decrease in the chances of developing high-level resistance to zidovudine. Both drugs were generally well tolerated.
authors.affiliation: Canadian HIV Trials Network, Vancouver, British Columbia, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Montaner
authors.forename: M T
authors.initials: MT
authors.lastname: Schechter
authors.forename: A
authors.initials: A
authors.lastname: Rachlis
authors.forename: J
authors.initials: J
authors.lastname: Gill
authors.forename: R
authors.initials: R
authors.lastname: Beaulieu
authors.forename: C
authors.initials: C
authors.lastname: Tsoukas
authors.forename: J
authors.initials: J
authors.lastname: Raboud
authors.forename: B
authors.initials: B
authors.lastname: Cameron
authors.forename: H
authors.initials: H
authors.lastname: Salomon
authors.forename: L
authors.initials: L
authors.lastname: Dunkle
authors.forename: L
authors.initials: L
authors.lastname: Smaldone
authors.forename: M A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D011446:Prospective Studies; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D015215:Zidovudine; D016049:Didanosine