title: Randomized, double-blind comparison of two nelfinavir doses plus nucleosides in HIV-infected patients (Agouron study 511).
abstract: OBJECTIVE
  To evaluate the safety and antiretroviral activity of nelfinavir mesylate at two doses as part of a combination regimen in HIV-infected, antiretroviral-naive patients.
  
  
  METHODS
  Phase III, multicenter, double-blind, placebo-controlled trial.
  
  
  METHODS
  Two-hundred and ninety-seven patients were randomized to one of three treatment groups: nelfinavir 750 mg three times daily (tid), nelfinavir 500 mg tid, or matching placebo, each in combination with open-label zidovudine (ZDV) 200 mg tid and lamivudine (3TC) 150 mg twice daily (bid). Data were analyzed on an intent-to-treat basis.
  
  
  RESULTS
  Sixty-seven percent of patients receiving nelfinavir 750 mg tid, and 50% receiving nelfinavir 500 mg tid in combination with ZDV/3TC achieved HIV RNA < 400 copies/ml compared to 7% receiving ZDV/3TC plus placebo (P < 0.001); 55% and 30% of patients in the nelfinavir-containing arms achieved HIV RNA < 50 copies/ml at week 24. This compared with 4% in the placebo-containing arm. For patients continuing nelfinavir treatment (750 mg or 500 mg tid as treated) for a further 6 months, the proportions achieving < 400 copies/ml at week 48 were 75% and 54% (P = 0.001) and < 50 copies/ml 61% and 37%, respectively (P = 0.004). The mean increases from baseline in CD4 cell counts were also durable in patients receiving the triple combination nelfinavir therapy. The range and incidence of adverse events was similar for the two nelfinavir-containing arms, with diarrhea being the most common adverse event.
  
  
  CONCLUSIONS
  Nelfinavir plus ZDV/3TC was superior to ZDV/3TC/placebo. In addition, the 750 mg tid nelfinavir dose was better than the 500 mg tid dose. Virologic responses were sustained over 12 months.
authors.affiliation: University of Alabama at Birmingham, Alabama 35294-2050, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Saag
authors.forename: P
authors.initials: P
authors.lastname: Tebas
authors.forename: M
authors.initials: M
authors.lastname: Sension
authors.forename: M
authors.initials: M
authors.lastname: Conant
authors.forename: R
authors.initials: R
authors.lastname: Myers
authors.forename: S K
authors.initials: SK
authors.lastname: Chapman
authors.forename: R
authors.initials: R
authors.lastname: Anderson
authors.forename: N
authors.initials: N
authors.lastname: Clendeninn
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D019888:Nelfinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019888:Nelfinavir