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

Objectives: To compare the efficacy and safety of two-times-daily versus th ree-times-daily indinavir in combination with zidovudine and lamivudine. De sign: Two multicenter, open-label, randomized 24-week studies. Methods: Adults HIV-1 infection, HIV-1 RNA greater than 10 000 copies/ml, a nd no prior lamivudine or protease inhibitor therapy were eligible. In a pi lot 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), pati ents received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subj ects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An in tent-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, bu t was prematurely discontinued when interim analysis suggested greater effi cacy 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-dai ly versus 64% receiving two-times daily indinavir (P < 0.01). Conclusion: Three-limes-daily indinavir appears more efficacious than two-t imes-daily dosing when administered with zidovudine and lamivudine. Two-tim es-daily indinavir dosing should only be considered in situations character ized by favorable pharmacokinetic drug-drug interactions. (C) 2000 Lippinco tt Williams & Wilkins.