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

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Abstract
Objectives: To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine. Design: Two multicenter, open-label, randomized 24-week studies.Methods: Adults HIV-1 infection, HIV-1 RNA greater than 10 000 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).Conclusion: Three-limes-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. (C) 2000 Lippincott Williams & Wilkins.Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37212 USAGuatemalan Assoc Prevent & Control AIDS, Clin Familiar Luis Angel Garcia, Guatemala City, GuatemalaAIDS Res Consortium Atlanta, Atlanta, GA USAUniv Estadual Campinas, Fac Ciencias Med, São Paulo, BrazilJohns Hopkins Univ, Baltimore, MD USAUniv São Paulo, São Paulo, BrazilUniv So Calif, Los Angeles, CA USAHosp Dr Sotero del Rio, Santiago, ChileUniversidade Federal de São Paulo, São Paulo, BrazilCONASIDA, Mexico City, DF, MexicoHosp Muniz, Buenos Aires, DF, ArgentinaHuesped Fdn, Buenos Aires, DF, ArgentinaUniv Texas, Galveston, TX 77555 USABaylor Coll Med, Houston, TX 77030 USAUniv Washington, Sch Med, Seattle, WA USAVet Adm Med Ctr, San Juan, PR USAMerck Res Labs, West Point, PA USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc