Fosamprenavir/ritonavir in advanced HIV disease (TRIAD): A randomized study of high-dose, dual-boosted or standard dose fosamprenavir/ritonavir in HIV-1-infected patients with antiretroviral resistance

Jean Michel Molina, Mounir Ait-Khaled, Roberto Rinaldi, Giovanni Penco, Jean Guy Baril, Roberto Cauda, Vicente Soriano, Gilles Pialoux, Mary Beth Wire, Yu Lou, Naomi Givens, Charles Craig, Garrett W. Nichols, Inês Barbosa, Jane Yeo, David Cooper, Nathan Clumeck, Sylvie Trottier, Graham Smith, Ken LogueBrian Conway, Christos Tsoukas, Maria Louisa Partisiani, Daniel Sereni, Alain Lafeuillade, Jean François Bergmann, Marie Aude Khuong-Josses, Olivier Bouchaud, Andreas Plettenberg, Panagiotis Gargalianos-Kakolyris, George Chrysos, Laura Sighinolfi, Francesco Mazzotta, Gaetano Filice, Pietro Caramello, Francisco Blanco, Pere Domingo, Vicente Estrada, Federico Pulido, Jose Alberto Terrón, Miguel Górgolas, Blai Coll, Joaquín Portilla, Margaret Johnson, Mia Huengsberg, Phillipa Easterbrook, Alan Winston

Research output: Contribution to journalArticlepeer-review

Abstract

Background: APV102002 was an open-label study comparing a dual-boosted HIV-1 protease inhibitor (PI) [fosamprenavir/lopinavir/ritonavir (FPV/ LPV/RTV; 1400 mg/533 mg/133 mg twice daily)] and a high dose of FPV/RTV 1400 mg/100 mg twice daily (HD-FPV/RTV) versus the standard FPV/RTV 700 mg/100 mg twice-daily (STD-FPV/RTV) regimen for 24 weeks. Methods: Adult patients with prior failure to two or more PI-based regimens and on a failing PI regimen were randomized to STD-FPV/RTV (n = 24), HD-FPV/RTV (n = 25) or FPV/LPV/RTV (n = 25). The primary aim was to test week 24 superiority of HD-FPV/RTV and FPV/LPV/RTV over STD-FPV/RTV as measured by plasma HIV-1 RNA average area under the curve minus baseline (AAUCMB). Results: There was no difference in the week 24 AAUCMB between the regimens. The proportion of patients with τ) was 49% higher in the HD-FPV/RTV arm than in the STD-FPV/RTV arm and similar in the FPV/LPV/RTV and STD-FPV/RTV arms. The plasma lopinavir Cτ was similar to historical data with standard LPV/RTV 400 mg/100 mg twice daily. All regimens were relatively well tolerated, although diarrhoea was more frequent in the HD-FPV/RTV and FPV/LPV/RTV arms, and hypertriglyceridaemia and increased total cholesterol were more common in the FPV/LPV/RTV arm. Conclusions: While the strategies of higher dose FPV/RTV and dual FPV/LPV/RTV were relevant at the time of study initiation, new therapies for antiretroviral-experienced patients make such strategies of limited interest. In addition, this study failed to demonstrate antiviral superiority of the HD-FPV/RTV or FPV/LPV/RTV regimen over the STD-FPV/ RTV twice-daily regimen in highly treatment-experienced patients.

Original languageEnglish
Pages (from-to)398-410
Number of pages13
JournalJournal of Antimicrobial Chemotherapy
Volume64
Issue number2
DOIs
Publication statusPublished - 2009

Keywords

  • Dual-boosted PIs
  • High-dose FPV/RTV
  • LPV/RTV
  • Multi PI-experienced
  • Protease inhibitors (PI)

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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