title: A phase II safety and efficacy study of amprenavir in combination with zidovudine and lamivudine in HIV-infected patients with limited antiretroviral experience. Amprenavir PROAB2002 Study Team.
abstract: OBJECTIVE
  To determine the safety and efficacy of amprenavir (APV) in combination with lamivudine (3TC) and zidovudine (ZDV).
  
  
  METHODS
  Multicenter, randomized, partially blinded trial.
  
  
  METHODS
  Nine study sites in the United States and Europe.
  
  
  METHODS
  A group of 84 HIV-infected subjects with no prior 3TC or protease inhibitor therapy experience, CD4 cell count > or = 150 x 10(6) cells/l, and plasma HIV RNA > 10000 copies/ml.
  
  
  METHODS
  3TC/ZDV with one of three doses of APV (900, 1050, or 1200 mg) versus 3TC/ZDV with 1050 mg placebo. All medications were dosed twice daily. The 1050 mg placebo and the APV 1050 mg dose were administered blinded. After 12 weeks, APV 1050 mg was substituted for 1050 mg placebo in the control group and the blind was maintained.
  
  
  METHODS
  Reduction in plasma HIV RNA from baseline; proportion of subjects with plasma HIV RNA < 400 copies/ml; and an increase in CD4 cell count from baseline.
  
  
  RESULTS
  During the initial 12-week study period, APV/3TC/ZDV-treated subjects had greater viral suppression than the group receiving two nucleosides. By 48 weeks, 89% of subjects in the group taking the highest APV dose (1200 mg) had plasma HIV RNA < 400 copies/ml while 42% of the 900 mg group and 60% of the 3TC/ZDV group (1050 mg APV added at week 12) had plasma HIV RNA < 400 copies/ml using an as-treated analysis. By 60 weeks, 86% of subjects in the APV 1200 mg group had plasma HIV RNA < 400 copies/ml in the as-treated analysis, while 25% (900 mg), 43% (1050 mg), and 20% (1200 mg) of subjects had viral load <400 copies/ml in a strict intent-to-treat analysis owing to treatment discontinuations. Median CD4 cell count increases at week 60 were highest for the three treatment groups who received APV throughout the study, by intent-to-treat and as-treated analyses. The most common adverse events considered to be possibly drug related were nausea, rash, oral paresthesia, diarrhea, and fatigue.
  
  
  CONCLUSIONS
  Treatment with APV, dosed at 1200 mg twice daily in combination with 3TC/ZDV, resulted in sustained viral suppression. This combination represents a potent alternative initial antiretroviral regimen for protease inhibitor-naive individuals.
authors.affiliation: University of California San Diego, USA.
authors.forename: R
authors.initials: R
authors.lastname: Haubrich
authors.forename: M
authors.initials: M
authors.lastname: Thompson
authors.forename: R
authors.initials: R
authors.lastname: Schooley
authors.forename: W
authors.initials: W
authors.lastname: Lang
authors.forename: A
authors.initials: A
authors.lastname: Stein
authors.forename: D
authors.initials: D
authors.lastname: Sereni
authors.forename: M E
authors.initials: ME
authors.lastname: van der Ende
authors.forename: F
authors.initials: F
authors.lastname: Antunes
authors.forename: D
authors.initials: D
authors.lastname: Richman
authors.forename: G
authors.initials: G
authors.lastname: Pagano
authors.forename: L
authors.initials: L
authors.lastname: Kahl
authors.forename: A
authors.initials: A
authors.lastname: Fetter
authors.forename: D J
authors.initials: DJ
authors.lastname: Brown
authors.forename: N
authors.initials: N
authors.lastname: Clumeck
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D002219:Carbamates; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D012367:RNA, Viral / Q000097:blood; D012449:Safety; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects*; D013997:Time Factors; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015215:Zidovudine / Q000008:administration & dosage*
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D019259:Lamivudine; D015215:Zidovudine; C095108:amprenavir