title: Virologic responses to a ritonavir--saquinavir-containing regimen in patients who had previously failed nelfinavir.
abstract: OBJECTIVE
  The effectiveness of a second protease inhibitor in patients who failed an initial protease inhibitor is unclear but believed to be low. It has been postulated, however, that patients who fail nelfinavir may respond differently. We therefore assessed the virologic response to a ritonavir-saquinavir-containing regimen in patients who had previously failed nelfinavir.
  
  
  METHODS
  A total of 26 patients enrolled in the nelfinavir clinical trials AG506 and AG511 at our two sites who failed (two consecutive HIV viral loads > 5000 copies/ml; branched DNA assay) were switched to a combination of stavudine 40 mg twice daily, lamivudine 150 mg twice daily, ritonavir 400 mg twice daily and saquinavir 400 mg twice daily.
  
  
  RESULTS
  The mean viral load at enrollment in this study was 46 674 copies/ml (range, 1075-146400 copies/ml). The median CD4 cell count was 222 x 10(6)/l (range, 82-448 x 10(6)/l). The median duration of nelfinavir use with a detectable viral load before the switch occurred was 48 weeks. Two patients discontinued the study at 3 weeks. All of the remaining patients (n = 24) reached undetectable viral loads (< 500 copies/ml) that were sustained at week 24 in 17 (71%) out of 24 subjects. The most frequent baseline mutations in the protease gene prior to switching were D30N (13 out of 18), N88D (eight out of 18) and M36I (eight out of 18). The presence or absence of these mutations was not predictive of a short-term virologic response.
  
  
  CONCLUSIONS
  Most patients who failed a nelfinavir-containing regimen responded to a switch to a combination regimen with saquinavir-ritonavir.
authors: Department of Medicine Washington University, St Louis, Missouri 63108, USA.
authors: P
authors: P
authors: Tebas
authors: A K
authors: AK
authors: Patick
authors: E M
authors: EM
authors: Kane
authors: M K
authors: MK
authors: Klebert
authors: J H
authors: JH
authors: Simpson
authors: A
authors: A
authors: Erice
authors: W G
authors: WG
authors: Powderly
authors: K
authors: K
authors: Henry
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D019888:Nelfinavir / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012367:RNA, Viral; D019438:Ritonavir / Q000627:therapeutic use*; D019258:Saquinavir / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D016333:HIV Protease; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir