title: Comparative studies of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine.
abstract: OBJECTIVE
  To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine.
  
  
  METHODS
  Two multicenter, open-label, randomized 24-week studies.
  
  
  METHODS
  Adults HIV-1 infection, HIV-1 RNA greater than 10000 copies/ml, and no prior lamivudine or protease inhibitor therapy were eligible. In a pilot study (Study A), patients received indinavir at 800 mg every 8 h, 1000 mg every 12 h, or 1200 mg every 12 h. In a subsequent study (Study B), patients received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subjects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An intent-to-treat analysis was used.
  
  
  RESULTS
  In Study A, which enrolled 88 patients, neither HIV-1 RNA nor CD4 cell responses differed significantly between treatment groups at 24 weeks when corrected for multiple comparisons. Study B enrolled 433 patients, but was prematurely discontinued when interim analysis suggested greater efficacy of three-times-daily indinavir. Of the first 87 patients reaching week 24, HIV-1 RNA was less than 400 copies/ml in 91% receiving three-times-daily versus 64% receiving two-times-daily indinavir (P < 0.01).
  
  
  CONCLUSIONS
  Three-times-daily indinavir appears more efficacious than two-times-daily dosing when administered with zidovudine and lamivudine. Two-times-daily indinavir dosing should only be considered in situations characterized by favorable pharmacokinetic drug-drug interactions.
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA. david.w.haas@vanderbilt.edu
authors.forename: D W
authors.initials: DW
authors.lastname: Haas
authors.forename: E
authors.initials: E
authors.lastname: Arathoon
authors.forename: M A
authors.initials: MA
authors.lastname: Thompson
authors.forename: R
authors.initials: R
authors.lastname: de Jesus Pedro
authors.forename: J E
authors.initials: JE
authors.lastname: Gallant
authors.forename: D E
authors.initials: DE
authors.lastname: Uip
authors.forename: J
authors.initials: J
authors.lastname: Currier
authors.forename: L M
authors.initials: LM
authors.lastname: Noriega
authors.forename: D S
authors.initials: DS
authors.lastname: Lewi
authors.forename: P
authors.initials: P
authors.lastname: Uribe
authors.forename: L
authors.initials: L
authors.lastname: Benetucci
authors.forename: P
authors.initials: P
authors.lastname: Cahn
authors.forename: D
authors.initials: D
authors.lastname: Paar
authors.forename: A C
authors.initials: AC
authors.lastname: White
authors.forename: A C
authors.initials: AC
authors.lastname: Collier
authors.forename: C H
authors.initials: CH
authors.lastname: Ramirez-Ronda
authors.forename: C
authors.initials: C
authors.lastname: Harvey
authors.forename: M O
authors.initials: MO
authors.lastname: Chung
authors.forename: D
authors.initials: D
authors.lastname: Mehrotra
authors.forename: J
authors.initials: J
authors.lastname: Chodakewitz
authors.forename: B Y
authors.initials: BY
authors.lastname: Nguyen
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir