title: Efficacy and safety of stavudine and didanosine combination therapy in antiretroviral-experienced patients.
abstract: OBJECTIVE
  To assess the efficacy, tolerance, and safety of combination antiretroviral therapy with didanosine and stavudine in HIV-infected patients with CD4+ cell counts > 100 x 10(6)/l and HIV plasma RNA > 10(4) copies/ml previously treated with other antiretroviral agents for at least 3 months.
  
  
  METHODS
  In this open, multicentre, non-randomized, Phase II pilot study, adult patients were administered didanosine (200 mg twice daily) plus stavudine (40 mg twice daily) for 6 months. Patients for whom the first regimen had led to undetectable HIV RNA levels were offered a second 6-month course of treatment; those who had achieved insufficient immunological and virological gains in the first 6 months were given a new combination.
  
  
  METHODS
  Primary evaluation of efficacy was based on viral load measured by branched DNA second-generation testing (lower limit of detection, 500 copies/ml) and CD4+ cell counts; secondary evaluations included AIDS-defining events and clinical side-effects.
  
  
  RESULTS
  Sixty-five patients with median prior antiretroviral therapy of 24 months (65 with zidovudine, 29 with zalcitabine) were included in the study. At baseline, median CD4+ cell count was 198 x 10(6)/l and median plasma HIV RNA was 80000 copies/ml (4.9 log10 copies/ml). In this heavily pretreated population, an increase in the mean CD4+ cell count was observed (+70 x 10(6)/l at 24 weeks). In addition, rapid and prolonged antiviral activity was seen, with a mean maximal decrease of 1.1 log10 copies/ml at week 4, a mean decrease of 0.89 log10 copies/ml at week 24, and a plasma RNA viraemia < 500 copies/ml achieved in 14% of patients at week 24.
  
  
  CONCLUSIONS
  Combination therapy with stavudine and didanosine is safe and leads to a sustained antiviral effect, even in patients with prolonged prior antiretroviral exposure and low CD4+ cell counts.
authors.affiliation: Department of Infectious Diseases, University Hospital, Nantes, France.
authors.forename: F
authors.initials: F
authors.lastname: Raffi
authors.forename: V
authors.initials: V
authors.lastname: Reliquet
authors.forename: S
authors.initials: S
authors.lastname: Auger
authors.forename: J M
authors.initials: JM
authors.lastname: Besnier
authors.forename: J M
authors.initials: JM
authors.lastname: Chennebault
authors.forename: E
authors.initials: E
authors.lastname: Billaud
authors.forename: C
authors.initials: C
authors.lastname: Michelet
authors.forename: P
authors.initials: P
authors.lastname: Perre
authors.forename: A
authors.initials: A
authors.lastname: Lafeuillade
authors.forename: T
authors.initials: T
authors.lastname: May
authors.forename: S
authors.initials: S
authors.lastname: Billaudel
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010865:Pilot Projects; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D016049:Didanosine