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

David W. Haas, Eduardo Arathoon, Melanie A. Thompson, Rogiero De Jesus Pedro, Joel E. Gallant, David E. Uip, Judith Currier, L. Miguel Noriega, David S. Lewi, Patricia Uribe, Jorge Benetucci, Pedro Cahn, David Paar, A. Clinton White, Ann C. Collier, Carlos H. Ramirez-Ronda, Charlotte Harvey, Mi Ok Chung, Devan Mehrotra, Jeffrey ChodakewitzBach Yen Nguyen

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24 Scopus citations

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-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. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)1973-1978
Number of pages6
JournalAIDS
Volume14
Issue number13
DOIs
StatePublished - Sep 8 2000

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Keywords

  • Antiretroviral therapy
  • Clinical trial
  • HIV infection
  • HIV protease inhibitors
  • Indinavir
  • Lamivudine
  • Viral load
  • Zidovudine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Haas, D. W., Arathoon, E., Thompson, M. A., De Jesus Pedro, R., Gallant, J. E., Uip, D. E., Currier, J., Noriega, L. M., Lewi, D. S., Uribe, P., Benetucci, J., Cahn, P., Paar, D., White, A. C., Collier, A. C., Ramirez-Ronda, C. H., Harvey, C., Chung, M. O., Mehrotra, D., ... Nguyen, B. Y. (2000). Comparative studies of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine. AIDS, 14(13), 1973-1978. https://doi.org/10.1097/00002030-200009080-00013