Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV

Ann C. Collier, Camlin Tierney, Gerald F. Downey, Susan H. Eshleman, Angela Kashuba, Karin Klingman, Emanuel N. Vergis, Gary E. Pakes, James F. Rooney, Alex Rinehart, John W. Mellors, George Bishopric, Barbara Brizz, Marlene Cooper, Linda Gideon, Nicole Grosskopf, Belinda Ha, Bernadette Jarocki, Ana Martinez, Jane ReidTrevor Scott, Nancy Tustin, Ed Acosta, Merissa L. Astley, Benigno Rodriguez, Patricia Walton, Judith Feinberg, Jenifer Baer, Luis M. Mendez, Frances Canchola, Michael F. Para, Laura Laughlin, Joseph J. Eron, Cheryl Marcus, Valery Hughes, Todd Stroberg, Brad Hare, Jody Lawrence, Daniel J. Skiest, Jesse Tarbutton, William A. O'Brien, Cheryl Mogridge, Karen Cavanagh, Charles Gonzalez, Hector H. Bolivar, Margaret A. Fischl, N. Jeanne Conley, Laura Olin, Mitchell Goldman, Beth Zwickl, Donna Mildvan, Donald Garmon

Research output: Contribution to journalArticle

Abstract

Purpose: To compare activity and safety of a regimen containing lopinavir/ritonavir (LPV/r) + fosamprenavir (FPV) to regimens with LPV/r or FPV + r and to test the hypothesis that a ritonavir-enhanced dual protease inhibitor (PI) regimen has better antiviral activity. Method: This study was a multicenter, open-label, randomized study. HIV-infected adults with prior PI failure were selectively randomized based on prior PI experience to either LPV/r, FPV + r, or LPV/r + FPV. All patients received tenofovir DF and 1 to 2 nucleoside reverse transcriptase inhibitors. Results: Baseline characteristics were similar across arms. Study enrollment and follow-up were stopped early (N = 56) because pharmacokinetic analyses showed significantly lower LPV and FPV exposures in the dual-PI arm. At Week 24, proportions achieving >1 log 10 decline in HIV RNA or <50 copies/mL in the dual-PI versus single-PI arms combined were 75% vs. 61% in intent-to-treat (ITT, p = .17) and 100% vs. 64% in as-treated (AT) analyses (p = .02), respectively. Median CD4+ T cell/mm3 increases were 81 vs. 41 (ITT, p = .4) and 114 vs. 43 (AT, p = .08), respectively. Clinical events and toxicity rates were not different between arms. Conclusion: The trial was unable to show a difference between dual versus single PIs in ITT analyses but favored dual PIs in AT analyses.

Original languageEnglish (US)
Pages (from-to)91-102
Number of pages12
JournalHIV clinical trials
Volume9
Issue number2
DOIs
StatePublished - Mar 1 2008

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Keywords

  • Antiretroviral therapy
  • Fosamprenavir
  • Lopinavir
  • Protease inhibitors
  • Ritonavir

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Collier, A. C., Tierney, C., Downey, G. F., Eshleman, S. H., Kashuba, A., Klingman, K., Vergis, E. N., Pakes, G. E., Rooney, J. F., Rinehart, A., Mellors, J. W., Bishopric, G., Brizz, B., Cooper, M., Gideon, L., Grosskopf, N., Ha, B., Jarocki, B., Martinez, A., ... Garmon, D. (2008). Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV. HIV clinical trials, 9(2), 91-102. https://doi.org/10.1310/hct0902-91