title: Low efficacy and high frequency of adverse events in a randomized trial of the triple nucleoside regimen abacavir, stavudine and didanosine.
abstract: BACKGROUND
  Highly active antiretroviral therapy containing three nucleoside reverse transcriptase inhibitors has been somewhat successful, but the clinical efficacy is unclear.
  
  
  METHODS
  Randomized, controlled, open-label trial of 180 antiretroviral drug-naive HIV-infected patients allocated to a regimen of abacavir, stavudine and didanosine (A/S/D, n = 60), ritonavir and saquinavir (R/S 400/400 mg twice daily; n = 60) or nelfinavir and nevirapine (N/N 1250/200 mg twice daily; n = 60); the latter two in combination with lamivudine and zidovudine. The primary endpoint was HIV plasma RNA < or = 20 copies/ml after 48 weeks.
  
  
  RESULTS
  At baseline, the median CD4 cell count was 161 x 106 cells/l (range, 0-920) and the HIV RNA was 5.0 log10 copies/ml (range, 2.7-6.7). At 48 weeks, 43% in the A/S/D arm had a HIV RNA < or = 20 copies/ml, compared with 69% in the N/N arm (P < 0.01) and 62% in the R/S arm (P < 0.05). In a multivariate analysis, the A/S/D arm had an odds ratio of obtaining a viral load of < or = 20 copies/ml at week 48 of 0.25 [95% confidence interval (CI) 0.10-0.59] versus N/N and 0.53 (95% CI, 0.33-0.83) versus R/S. The A/S/D arm had a particularly poor outcome in patients with higher viral load and AIDS at baseline: 63% had to discontinue A/S/D (any drug). Side effects were more frequent in the A/S/D arm and included neuropathy 27%, suspicion of hypersensitivity 12%, and increase in lactate accompanied by systemic symptoms 8%.
  
  
  CONCLUSIONS
  The A/S/D regimen had a low efficacy and a high frequency of adverse events and cannot be recommended.
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D018791:CD4 Lymphocyte Count / Q000379:methods; D016049:Didanosine / Q000008:administration & dosage* / Q000009:adverse effects; D015224:Dideoxynucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007773:Lactates / Q000097:blood; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000008:administration & dosage / Q000009:adverse effects; D009422:Nervous System Diseases / Q000139:chemically induced; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects; D019258:Saquinavir / Q000008:administration & dosage / Q000009:adverse effects; D018119:Stavudine / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D016049:Didanosine; D015224:Dideoxynucleosides; D007773:Lactates; D019888:Nelfinavir; D019829:Nevirapine; D012367:RNA, Viral; D019438:Ritonavir; D019258:Saquinavir; D018119:Stavudine; D000099227:Abacavir