Comparative studies of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine

Authors:
  • EAEduardo Arathoon
    Eduardo Arathoon
  • MTMelanie A Thompson
    Melanie A Thompson
  • RPRogiero de Jesus Pedro
    Rogiero de Jesus Pedro
  • JGJoel E Gallant
    Joel E Gallant
  • DUDavid E Uip
    David E Uip
  • JCJudith Currier
    Judith Currier
  • LNL. Miguel Noriega
    L. Miguel Noriega
  • DLDavid S Lewi
    David S Lewi
  • PUPatricia Uribe
    Patricia Uribe
  • JBJorge Benetucci
    Jorge Benetucci
  • PCPedro Cahn
    Pedro Cahn
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Abstract
To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine. Two multicenter, open-label, randomized 24-week studies. 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. 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). 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.

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